Indian Pediatrics October 2020 Issue

E-copy
VOLUME 57
NUMBER 10
OCTOBER 2020
Copyright of Indian Pediatrics.

It is meant for personal use only, and not to be shared widely over social media platforms, blogs and mass e-mails.
ADVERTISEMENT
INDIAN PEDIATRICS 883 VOLUME 57__OCTOBER 15, 2020

ADVERTISEMENT

Indian
Pediatrics
October 2020 Volume 57 Number 10
Editor-in-Chief Devendra Mishra CONTENTS

Executive Editor Siddarth Ramji
Managing Editor Rakesh Lodha PRESIDENT’S PAGE
Associate Editors Anup Mohta
Pooja Dewan dIAP: Knowledge Sharing Amidst the Pandemic
Joseph L Mathew –BAKUL JAYANT PAREKH AND ARUN BANSAL 887
Aashima Dabas
Executive Members Abhijit Saha PERSPECTIVE
JS Kaushik
Sunita Bijarnia Sudden Unexpected Death in Epilepsy (SUDEP) - What Pediatricians
Rachna Seth Need to Know–DIVYANI GARG AND SUVASINI SHARMA 890
Somshekhar Nimbalkar
Sanjay Verma EDITORIAL COMMENTARIES
Kirtisudha Mishra
Ashish Jain Refining Clinical Triage and Management of Dengue Infection in
Kana Ram Jat Children: A Timely Approach–ANITA SHET AND KAYUR MEHTA 895
Sumaira Khalil
Romit Saxena Identifying India’s Dual Nutrition Burden: Role of Body Mass
International Advisory Board Index Quick Screening Tool–SANGITA YADAV 897
Prashant Mahajan (USA)
Sanjay Mahant (Canada) RESEARCH PAPERS
PSN Menon (Kuwait)
John M Pettifor (South Africa) WHO 2009 Warning Signs as Predictors of Time Taken for Progression
SudhinThayyil (UK) to Severe Dengue in Children–PRIYA SREENIVASAN, S GEETHA AND
Gaurishankar Shah (Nepal)
A SANTHOSH KUMAR 899
National Advisory Board
Central Zone Gouri Passi Body Mass Index Quick Screening Tool for Indian Academy of
Pawan Kalyan Pinnamaneni
East Zone Sudip Dutta
Pediatrics 2015 Growth Charts–VAMAN KHADILKAR, NIKHIL LOHIYA,
Apurba Ghosh SHASHI CHIPLONKAR AND ANURADHA KHADILKAR 904
North Zone Sourabh Dutta
Raj Kumar Gupta Progression of Thyrotropinemia in Overweight and Obese Children
South Zone Subramanya NK From Puducherry, India–SRINIVASAN THIAGARAJAN, THIRUNAVUKKARASU
Rajeev K Zachariah ARUN BABU AND RAJESHWAR BALAJI 908
West Zone Mahesh A Mohite
Paresh Thakker Weight of Schoolbags Among Indian Schoolchildren in Pune and
Chief Advisor AP Dubey Hyderabad–RAJNEESH K JOSHI, SAURABH MAHAJAN, A YASHOWANTH RAO,
Central IAP Advisors Bakul J Parekh
Piyush Gupta
LIKITH POLISETTY AND MADHURI KANITKAR 910
S Thangavelu Epidemiological and Clinical Characteristics of COVID-19 in Indian
GV Basavaraj (Ex-officio)
Biostatistics Amir Maroof Khan Children in the Initial Phase of the Pandemic–BHAKTI SARANGI, VENKAT
Rajeev Malhotra SANDEEP REDDY, JITENDRA S OSWAL, NANDINI MALSHE, AJINKYA PATIL,
Electronic Media Sanjeev Goel MANOJIT CHAKRABORTY AND SANJAY LALWANI 914
Ethics Arun Gupta
Office Matters Peeyush Jain Maternal Occupational Tobacco Exposure and Newborn Umbilical
Chandramohan Kumar Cord Serum Leptin Concentration–SWATHI S RAO, A PREETHIKA,
Publication AS Vasudev
SangitaYadav
DENYA MARY YELDHO, Y SUNIL KUMAR AND RATHIKA D SHENOY 918
Social Media Dinesh Mittal Role of Flexible Bronchoscopy in Ventilator-Dependent Neonates
Jerin C Sekhar
Website C Vidyashankar –JAVEED IQBAL BHAT, BASHIR A CHAROO, SHIHAB ZAHOOR, QAZI IQBAL AHMAD
Amit P Shah AND AMBREEN ALI AHANGAR 922
885
CONTENTS (contd.)
Validation of the Testicular Workup for Ischemia and Suspected Torsion (TWIST) Score in the
Diagnosis of Testicular Torsion in Children With Acute Scrotum–PRADYUMNA PAN 926
SPECIAL PAPERS
Hyperinflammatory Syndrome in Children Associated With COVID-19: Need for Awareness
–CHANDRIKA S BHAT, LATIKA GUPTA, S BALASUBRAMANIAN, SURJIT SINGH AND ATHIMALAIPET V RAMANAN 929
Cardiac Involvement in Children With COVID-19–UTKARSH KOHLI AND RAKESH LODHA 936
REVIEW ARTICLE
Medical Expulsive Therapy for Urinary Stone Disease in Children
–SELASIE Q GOKA AND LAWRENCE COPELOVITCH 940
MEDICAL EDUCATION
Training-Module for Residents in Medical Educational Technologies (TRIM): Need and Operational
Strategies–RAJIV MAHAJAN, PIYUSH GUPTA AND TEJINDER SINGH 944
A Road Map for Simulation Based Medical Students Training in Pediatrics: Preparing the Next
Generation of Doctors–GEETHANJALI RAMACHANDRA, ELLEN S DEUTSCH, AND VINAY M NADKARNI 950
REMINISCENCES FROM INDIAN PEDIATRICS: A TALE OF 50 YEARS
Half a Century With Pediatric Viral Encephalitis–ROMIT SAXENA AND ANNESHA CHAKRABORTI 957
UPDATES
Identification, Evaluation, and Management of Children With Autism Spectrum Disorder:
American Academy of Pediatrics 2020 Clinical Guidelines–SHARMILA BANERJEE MUKHERJEE 959
RESEARCH LETTERS
A Preliminary Report of COVID-19 in Children in India– SOURAV BANERJEE, ARITRA GUHA, AVISHIKTA DAS,
MOUSAMI NANDI AND RAKESH MONDAL 963
Effect of Robot-Assisted Gait Training on Selective Voluntary Motor Control in Ambulatory Children
with Cerebral Palsy–DRAGANA ZARKOVIC, MONIKA SORFOVA, JAMES J TUFANO, PATRIK KUTILEK, SLAVKA VITECKOVA,
KATJA GROLEGER-SRSEN AND DAVID RAVNIK 964
Pediatric Papilledema at a Tertiary Care Ophthalmological Center–MURUGESAN MAHESWARAN,
MULASTHANAM SAI DHEERA, MAHESH KUMAR AND AKKAYASAMY KOWSALYA 966
Noonan Syndrome in Thai Children–NONGLAK BOONCHOODUANG, ORAWAN LOUTHRENOO AND PRANOOT TANPAIBOON 967
CLINICAL CASE LETTER
COVID-19 in a Child With Diabetic Ketoacidosis: An Instigator, a Deviator or a Spectator
–SANILA DANIEL, BHUSHIT GADHIYA, AKANKSHA PARIKH AND PREETHA JOSHI 969
CORRESPONDENCE 971
NEWS IN BRIEF 981
CLIPPINGS 982
IMAGE 983
BOOK REVIEW 983
ADVERTISEMENTS 882-84,894,913,921,925,935,970,984-88
Address for ordinary letters: The Editor-in-Chief, Indian Pediatrics, P. Box No. 3889, New Delhi-110 049.
Address for registered/speed post letters: Dr. Devendra Mishra, Editor-in-Chief, Indian Pediatrics,
115/4, Ground Floor, Gautam Nagar, New Delhi 110 049, India. Tel: (011) 46052593
E-mail: jiap@nic.in; Website: www.indianpediatrics.net; Facebook: www.facebook.com/Indianpediatrics;
Twitter: @EditorIndPed; Instagram: @indianpediatrics
886
PRESIDENT’S PAGE
dIAP: Knowledge Sharing Amidst the Pandemic

BAKUL JAYANT PAREKH1* AND ARUN BANSAL2
1President and 2EB Member, Indian Academy of Pediatrics 2020
*bakulparekh55@gmail.com
T
his year has been a year of firsts for the Indian Worldwide, it has been recognized that while it is
Academy of Pediatrics (IAP). It started two important to provide patient care, it is also necessary to
years ago, when you all elected me as the ensure adequate training and teaching of medical students
President elect of our mother organization IAP, who are future physicians. But the logical and practical
unopposed – first time in the history of IAP in last four concerns of patient safety remain, as these students may
decades. This shows the faith and affection you all have act as asymptomatic carriers of SARS-CoV-2 (Severe
for me, and honestly, that has left me greatly humbled. It acute respiratory syndrome – Coronavirus 2).
motivated me to go the extra mile to achieve the best for Technology has come to our rescue to continue edu-
our mother organization IAP. I had a vision which would cation through the digital platform. Medical education
change the way that our medical fraternity works, and has transformed through the use of online media for
benefit our many fellow pediatricians who are generally virtual team meetings, clinical skills learning, and even
practicing in the remote locations and rural areas. The for conducting examinations. Many medical colleges
dIAP platform – a technology driven academy – was have converted their usual classroom teaching to the e-
established for the first time. With dIAP we reached the learning platform using various applications available for
unreached, taking whatever the IAP has to offer to every online classes and webinars. As most of the teaching
corner of our country and beyond. hospitals cater to a massive burden of patients and most
of the teaching staff is involved in clinical work, it allows
None of us were prepared for what happened next.
them lesser time to dedicate for teaching. Also, the senior
COVID-19 struck – an epidemic of global proportions!
faculty is actively involved in administrative issues like
Before the financial year ended, India was forced into a
ensuring preparedness for managing the pandemic
lock-down situation. Academics became a secondary
efficiently on a large scale.
require-ment – survival was of utmost importance. We,
the Doctors and the healthcare industry started working Keeping these points in mind, the Indian Academy of
overtime, trying to prevent the spread and find a cure, to Pediatrics has rightly introduced digital lectures, by the
help people survive. This was the time for IAP to come to name of Digital-IAP (dIAP), to facilitate e-learning in all
the rescue of members and community to continue its spheres of pediatrics. The dIAP team was already working
academics, social and community activities. No one knew quite hard. As the pandemic spread, they needed to pull up
what to do. Desperate times called for desperate mea- their socks and ensure that they could deliver well before
sures. We had to start thinking of different ways and so the expected timeline. I am happy to say that IAP was
called ‘new norms’. Physical distancing, the necessity to amongst the first organizations to start the webinar concept
use masks, and avoidance of close contact led many to on such a large scale. It was and still is hugely popular.
search for ‘work from home’ options. Likewise, students People across the country have started viewing and
in various disciplines are being taught by dedicated absorbing the knowledge shared in these webinars.
teachers using the online platform. Medical students, Knowledge was not only limited to COVID-19 and other
both undergraduates and postgraduates are allowed academic topics, but rather a holistic approach was taken
limited or no bedside learning time to avoid unnecessary to ensure the best interests of our members requirements
exposure. Apart from the routine work done by like teleconsultation solution, health and death insurance,
postgraduates in wards, where they learn practical skills, medicolegal support, COVID-19 guidelines, connecting
formal teaching activity has mainly remained restricted. with government, charitable and social responsibilities,
Grand rounds, combined teaching from faculty, and and so on. These sessions are being conducted daily,
bedside case presentations have come to a halt. Seminars including topics from all sub-specialties and cover the
with PowerPoint presentations involving large gathe- curriculum of postgraduate teaching. dIAP is freely
rings in the departments have also been suspended. accessible to all, and daily reminders are sent to IAP

PRESIDENT’S PAGE
members via social media and registered email IDs. Apart Alder Hey academy global pediatric lecture series
from live streaming, an option to view the recorded (GPLS), thereby allowing an opportunity for Indian
version has been made available in the archives. Webcast students and pediatricians to participate in distinguished
attendees may actively participate in these sessions, ask lectures overseas. IAP has also come up with the unique
queries, and share opinions using the chat box or direct concept of conducting online conferences through dIAP.
communication in personal meetings. The zonal meetings of IAP are being conducted by the
name of ‘PediWeek’. Each zone was given one week, and
IAP has conducted 422 online sessions from March 16,
this activity was a huge hit and has been appreciated by
2020 to August 31, 2020, with an overwhelming response
one and all. It was a mix of scientific and cultural
in each of these sessions from all over India (Fig. 1).
activities. All pediatricians and members of IAP had
Twenty-three (5%) sessions were conducted during the
actively participated in these PediWeeks.
morning hours (9 AM to 12 PM), 278 (66%) sessions in the
afternoon (1 PM to 4 PM), and 121 (29%) sessions in the The dIAP sessions have helped in reaching students,
evening (4 PM onwards). A total of 7,71,375 views with an private practitioners, and pediatricians at various hos-
average of 1886 views per session have been documented. pitals, who have benefitted from these classes. The online
The specialty-wise distribution is shown in Fig. 2. Twenty- learning archives could form a database for teaching in
three (5%) of these sessions were directly or indirectly the future. There have been some sessions involving
related to COVID-19, and the postgraduate clinics on parents where they join hands with the pediatricians for
Thursdays constituted 20 (4.7%) of these sessions. The the wellbeing of the children. dIAP has brought the
Pediatric Intensive Care Chapter of IAP has begun the teaching to your homes; it is eco-friendly, paperless,
PICU e-Gurukul program, in which weekly lectures are saves travel and a lot of time. Moreover, all the sessions
taken by stalwarts in the field of critical care. They have are recorded, and one can watch them at their
also started P2P PICU Febinar (Peer-to-Peer PICU convenience.
Fellows’ Webinar), providing a national platform for the
However, it also has a few disadvantages inherent to
pediatric intensive care fellows to present, teach and learn
the online platform (Fig. 3). Literature on the impact of the
from each other. It is a program ‘Of the Fellows, By the
pandemic on online medical education has flagged
Fellows, For the Fellows.’ The IAP respiratory chapter has
communication and student assessment problems,
started ‘Respinars’ for pulmonology teaching, in which the
technology-related issues, and difficulties in time
experts of the field take lectures.
management in these sessions. Despite these challenges
Similarly, each zone/state wing of IAP has also and technophobia, a majority have been able to achieve the
formulated their teaching/academic sessions online. expertise quickly to conduct digital classes. Another
dIAP has also partnered with the NHS UK through the drawback is that it has decreased the personal touch and
Fig.1 Trend of webinar numbers over the weeks.

PRESIDENT’S PAGE
Fig. 2 Sub-specialty distribution of online teaching sessions on the dIAP platform.
Fig. 3 Features of an online platform.
warmth, which was there during the physical meetings. To able best to adapt and adjust to the changing
overcome the various problems, IAP has come up with environment in which it finds itself.” Online learning is
specific solutions like facilitating 24-hour teaching the new way of life that we must adapt to in the days and
modules with feedback for practical learning. The BLS weeks to come, which has been put into action by IAP.
(Basic life support) and ALS (Advanced Life Support) I would like to personally thank Dr. Arun Bansal, Dr
modules have been remodeled to suit e-learning. dIAP is G V Basavaraj and Dr Namita Ravikumar who have spent
also planning to include the live answers from the audience their valuable time and effort to come up with the facts
during the lectures through the e-notepad. With this and figures pertaining to the different aspects in this
software, the audience can easily select one of the options document, making it an interesting and informative read.
given by the speaker. This year of the pandemic will I also hope that we can achieve even greater heights by
culminate with the highlight activity of IAP, i.e., the having a common goal – to enhance childcare in our
National PediWeek – dIAP will be conducting a virtual country and ensure that IAP becomes a well-known
national conference which will take virtual teaching to a organization, not just across the country, but rather across
different level. the entire world. Let us strive to make the best of these
Charles Darwin said, “it is not the most intellectual of trying times and ensure the best for our mother
the species that survives; it is not the strongest that organization.
survives, but the species that survives is the one that is Jai Hind! Jai IAP!

PERSPECTIVE
Sudden Unexpected Death in Epilepsy (SUDEP) - What Pediatricians

Need to Know
DIVYANI GARG1 AND SUVASINI SHARMA2
From the Departments of 1Neurology and 2Pediatrics, Lady Hardinge Medical College, New Delhi, India.
Correspondence to: Dr Suvasini Sharma, Associate Professor, Department of Pediatrics, Lady Hardinge Medical College and
associated Kalawati Saran Children’s Hospital, New Delhi 110 001, India. sharma.suvasini@gmail.com
Sudden unexpected death in epilepsy (SUDEP) is a devastating complication in children with epilepsy. Children with generalized tonic-
clonic convulsions, nocturnal seizures, and co-morbid developmental delay/intellectual disability are at higher risk of SUDEP. The
pathogenic mechanisms are incompletely understood and involve cardiac, respiratory, autonomic and cerebral dysfunction. Prone
positioning is also significantly associated with SUDEP and may be a target for SUDEP prevention. Good epilepsy control also attenuates
the risk; hence, it is important to provide adequate antiepileptic drug therapy with stress on drug compliance as well as early surgical
referral for seizure control, wherever necessary. It is recommended that parents of children with epilepsy be counseled about the risk
factors for SUDEP and potential measures of SUDEP prevention. We herein provide a pediatric perspective of the problem and guidance
about parental counselling for its prevention.
Keywords: Counselling, Morbidity, Outcome, Prevention, Uncontrolled epilepsy.
Published online: June 12, 2020; PII: S097475591600192
M
ortality in children with epilepsy is children compared to adults, the American Academy of
significantly higher than the general Neurology (AAN) practice guidelines on SUDEP
population [1]; although, most deaths in established the incidence rate of SUDEP in children with
children with epilepsy are not related to epilepsy to be 0.22/1000 patient–years (95% CI 0.16-
seizures or epilepsy [2]. The higher risk is explained by 0.31) after a systematic review of 12 class I studies [8].
several factors: respiratory illness with underlying Due to imprecision in incidence data results, random-
neurological condition that presents with seizures, effect meta-analysis was further performed. SUDEP was
systemic comorbidities, indirect factors as well as deaths found to affect 1 in 4,500 children with epilepsy in one
presumably or demonstrably due to seizures. Sudden year, making the risk of SUDEP rare.
unexpected death in epilepsy (SUDEP), which belongs to
the last group, has gained prominence as a cause of death Risk Predictors
in epilepsy in recent years. There are very few studies assessing risk factors in
DEFINITION childhood SUDEP and most of the data is derived from
larger studies in adults.
SUDEP is defined as a “sudden unexpected witnessed or
unwitnessed, non-traumatic, non-drowning death in a • The presence and frequency of generalized tonic-
patient with epilepsy with or without evidence of a clonic seizures (GTCS) is an important risk predictor
seizure and excluding documented status epilepticus in for SUDEP [8].
which post-mortem examination does not reveal a • The relative risk of SUDEP is 7.7 times higher in
toxicological or anatomical cause of death [3].’’ This patients with onset of epilepsy between 0-15 years
definition requires a postmortem examination to compared to onset after the age of 45 years [9].
diagnose SUDEP, which is not available in the majority
of instances. Hence, criteria have been described for • All-cause mortality, including SUDEP, is also higher
definite, probable and possible SUDEP [4] (Box I). in children with developmental delay [10].
BURDEN • Children with uncontrolled seizures have a higher risk
[11].
The incidence rates of SUDEP in children have been
reported to be 0.36-0.43 per 1000 person-years [5-7]. • SUDEP has also been shown to increase with the
Although SUDEP rates have been reported to be lower in duration and severity of seizures, with 15-fold risk

GARG & SHARMA SUDEP IN CHILDREN
include effects of long-standing seizure disorder such as

Box I Classification and Definition of Subtypes
of Sudden Unexpected Death in Epilepsy altered autonomic function, etiology of epilepsy (e.g.
(SUDEP) symptomatic, familial), factors related to drug therapy
such as abrupt withdrawal or polypharmacy etc. A
Definite SUDEP triggering seizure leads to preterminal events including
• Sudden, unexpected, witnessed or unwitnessed, cardiac, respiratory, autonomic and cerebral dysfunction.
non-traumatic and non-drowning death, occurring The various mechanisms (Fig. 1) include the following:
in benign circumstances, in an individual with
epilepsy, with or without evidence for a seizure, Cardiac dysfunction: Sudden cardiac arrest is a proposed
and excluding documented status epilepticus in mechanism with certain ion channel abnormalities being
which postmortem examination does not reveal implicated in both epilepsy and cardiac arrhythmia. The
a cause of death. most widely implicated is the sodium channel abnor-
Probable SUDEP mality, which may also explain the higher rates of SUDEP
in Dravet syndrome [17]. Another link is the association
• Same as definite SUDEP but without autopsy. between long QT syndrome and familial epilepsies, both
The victim should have died unexpectedly while
of which are channelopathies.
in a reasonable state of health, during normal
activities, and in benign circumstances, without Respiratory dysfunction: Severe peri-ictal hypoxia occurs
a known structural cause of death. in one-fourth of patients with SUDEP [17]. Autopsy
Possible SUDEP changes of pulmonary edema have also been observed in
SUDEP cases, but this is likely an effect than a cause of
• SUDEP cannot be ruled out but a competing
cause of death is present. If a death is witnessed, SUDEP.
a cutoff of death within one hour from acute Autonomic dysfunction: Various autonomic abnor-malities
collapse is suggested.
have been described in patients with refractory epilepsy
and include lower parasympathetic and higher sympathetic
tone, increased vasomotor tone and impaired heart rate
with more than 50 GTCS per year, nocturnal seizures variability [18]. Changes in ictal heart rate also suggest
and the occurrence of GTCS [12], as well as prolonged autonomic dysfunction, with tachycardia occur-ring in up
tonic state leading to post-ictal immobility [13]. to 60% of seizures and bradycardia in 6% of focal seizures
• Postictal generalized EEG suppression beyond 50 [17,19]. As per the Mortality in epilepsy monitoring units
seconds also may have a predictive role in SUDEP and study (MORTEMUS), an initiative that assessed cases of
is associated with sleep, shorter duration of clonic SUDEP and near-SUDEP in patients admitted for video-
phase, symmetric tonic extension posturing and EEG monitoring, post-ictal centrally mediated cardiac and
terminal burst-suppression after a seizure [14]. respiratory depression associated with post-ictal
generalized EEG suppression was a strong mechanism
• Symptomatic epilepsy has a higher risk of SUDEP leading to SUDEP [20]. The switch from parasympathetic
compared to idiopathic generalized epilepsy. Patients to sympathetic state, combined with sympathetic over-
with Dravet syndrome are also at a higher risk of death drive that accompanies the state of drug withdrawal that
[15]. accompany seizures may be a possible precipitant.
SUDEP shares certain features with the syndrome of Channelopathies: Channelopathies are disorders
sudden infant death (SIDS), suggesting possible common characterised by dysfunction of ion channels. Traditio-
mechanisms. SIDS is sudden and unexpected death that nally channelopathies have been considered genetic
occurs in infants below the age of one year. Both SIDS defects eg., long QT syndrome and Dravet syndrome. In
and SUDEP are diagnoses of exclusion, and autopsy inherited channelopathies, the same ion channel
findings are usually not revelatory. Deficiency in arousal abnormalities are expressed in the heart as well as the
response to rise in carbon dioxide in both syndromes may brain. Hence, these epilepsies are associated with an
contribute to death, suggesting that these two entities may arrythmia-prone cardiac condition.
lie on a continuum [16].
Recently, there is an emerging concept of acquired
PATHOPHYSIOLOGY
channelopathy i.e., channel dysfunction in patients with
The pathophysiology of SUDEP is not well elucidated chronic epilepsy. Animal studies have shown that
and is believed to arise from an interaction between epilepsy alters the expression of sodium, potassium,
predisposing factors and triggers. Predisposing factors calcium and cationic channels in the heart. In these

Seizure
↓
Spread to amygdala
↓
Midbrain/medulla inhibition
→
↓ Apnea
→ Loss of arousal
↑
↓
Hypoxia
Respiratory dysfunction
Cardiac dysfunction ↓ - Prone positioning
- Inherited/ acquired channelopathy Arrhythmia - Intrinsic pulmonary issues
- Intrinsic cardiac dysfunction ↓ - Sleep apnea
Autonomic dysfunction
↓
SUDEP
Fig. 1 Various pathophysiological mechanisms leading to sudden unexpected death in epilepsy (SUDEP).
acquired cardiac channelopathies, epilepsy increases the In terms of preventive drug therapy, it has been
pro-arrhythmic state increasing predisposition to sudden observed in mouse models of SUDEP that selective
death [21]. serotonin reuptake inhibitors (SSRI) such as fluoxetine
may decrease apnea risk [26]. Serotonergic neurons in the
Cerebral dysfunction: SUDEP occurs more often in sleep
brainstem are believed to be responsive to rise in CO2 and
and almost all cases are nocturnal and associated with the
fall in pH levels in the blood and thereby stimulate
prone position. Various neurotransmitter abnormalities
respiration and arousal. In a retrospective study on adults
have been reported in association with SUDEP including
with focal seizures [27], it was noted that patients on
low serotonin state [22] and excessive opioid [23] and
SSRIs (for co-morbid mental health problems) had a
adenosine activity. Brainstem serotonin modulates
reduced likelihood of post-ictal oxygen desaturation as
respiratory drive and has also been implicated in sudden
compared to patients who were not on SSRIs. Recently,
infant death syndrome [24]. It may contribute to SUDEP
two randomized controlled trials have been completed to
by a similar mechanism.
evaluate the role of fluoxetine to prevent post-seizure
INTERVENTIONS FOR PREVENTION apneas and desaturation; however, the results have not
been published yet. Massive release of endogenous
As uncontrolled epilepsy is a known risk factor, effective
opioids and adenosine is induced by seizures and helps in
epilepsy treatment to reduce frequency and duration of
seizure termination [28]. However, this surge can also
seizures as well as GTCS should be targeted. Nocturnal
lead to post-ictal apnea. Naloxone is currently under a
supervision was found to be protective in one case-
randomized trial for this purpose. Adenosine antagonists
control study [25] and may be combined with seizure
may also be beneficial for this purpose.
detection devices, but clinching evidence in SUDEP
prevention is lacking. It is of potential benefit in children These therapies; however, are still in the emerging
with uncontrolled or nocturnal seizures. In India, phase and currently being tried in adults. More evidence
nocturnal supervision of children is generally culturally is needed before the data can be extrapolated to children.
acceptable as co-sleeping of children with their parents is
Parental Counseling
common. A blanket ‘back to sleep’ advice to avoid prone
positioning may be recommended, with the caveat that it Counseling of caregivers and sensitization towards
is the post-ictal turning prone which is usually SUDEP is imperative. Caretakers should be educated
responsible. Hence parents should be counseled to turn regarding the importance of adherence to treatment,
the child to a lateral position and avoid prone position nocturnal supervision, especially to avoid prone position
after the seizure. The use of lattice or safety pillows may after seizures, as well as basic life support training
reduce the contribution of prone position to post-ictal imparted to willing caregivers. However, whether all
cardiorespiratory distress. patients with epilepsy should be counseled about the risk

of SUDEP or only high-risk patients remains a matter of Contributors: DG performed the literature review and wrote the
debate, and scientific data till date does not permit the first draft which was critically revised by SS. Both authors
establishment of evidence-based guidelines for the same. approved the final version of the submitted manuscript.
However, disclosure of SUDEP risk to all epilepsy Funding: None; Competing interest: None stated.
patients has been endorsed by multiple neurological REFERENCES
societies, including a joint task force of the American 1. Appleton R. Mortality in paediatric epilepsy. Arch Dis
Epilepsy Society and the Epilepsy Foundation and the Child. 2003;1091-4.
American Academy of Neurology (AAN) [29], and in 2. Gaitatzis A, Johnson AL, Chadwick DW, Shorvon SD,
India by the joint consensus document on parental Sander JW. Life expectancy in people with newly
counseling by Association of Child Neurology (AOCN) diagnosed epilepsy. Brain. 2004;127:2427-32.
and Indian Epilepsy Society (IES) [30]. In a study on 3. Nashef L. Sudden unexpected death in epilepsy:
Terminology and definitions. Epilepsia. 1997;38:S6-8.
parental views regarding the counseling of SUDEP risk,
4. Nashef L, E. So P. Ryvlin T. Tomson. Unifying the
parents generally expressed a preference for receiving definitions of sudden unexpected death in epilepsy.
routine SUDEP counseling at the time of the diagnosis of Epilepsia. 2012;53:227-33.
epilepsy [31]. In another study from Malaysia (32% of 5. Sillanpää M, Shinnar S. Long-term mortality in childhood-
participants were of Indian origin), 70.9% of parents felt onset epilepsy. N Engl J Med. 2010;363:2522-9.
that receiving SUDEP information was positive [32]. 6. Weber P, Bubl R, Blauenstein U, Tillmann BU, Lütschg J.
Most parents did not report any impact on their own Sudden unexplained death in children with epilepsy: A
functioning. However, increasing numbers over time cohort study with an eighteen-year follow-up. Acta
reported an impact on the child’s functioning. In a study Paediatr. 2005;94:564-7.
7. Sillanpää M, Shinnar S. SUDEP and other causes of
from UK, 74% of pediatric neurologists conveyed
mortality in childhood-onset epilepsy. Epilepsy Behav.
SUDEP information to a select group of patients only. In 2013;28:249-55.
contrast, 94% of parents of children with epilepsy 8. Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH,
expected the physician to provide SUDEP information Donner E, et al. Practice Guideline Summary: Sudden
[33]. Unexpected Death in Epilepsy Incidence Rates and Risk
Factors. Report of the Guideline Development, Dissemi-
In India, many neurologists and pediatricians feel that nation, and Implementation Subcommittee of the American
imparting the knowledge of SUDEP may increase Academy of Neurology and the American Epilepsy
parental anxiety and stress levels, which may be Society. Neurology. 2017;88:1674-80.
unwarranted as the complication is so rare. However, it is 9. Berg AT, Nickels K, Wirrell EC, Geerts AT, Callenbach
also known that many parents are afraid their child would PM, Arts WF, et al. Mortality risks in new-onset childhood
die when they witness the child having a seizure for the epilepsy. Pediatrics. 2013;132:124-31.
first time. The information that the risk of death is very 10. Shinnar S, Pellock JM. Update on the epidemiology and
prognosis of pediatric epilepsy. J Child Neurol. 2002; 17:
low may be reassuring. Also, the knowledge of this
S4-S17.
condition may improve drug compliance, as seen in 11. Nickels KC, Grossardt BR, Wirrell EC. Epilepsy-related
studies from outside India. In an Indian study of SUDEP mortality is low in children: A 30-year population-based
counseling of adults with epilepsy and their caregivers, it study in Olmsted County, MN. Epilepsia. 2012;53:2164-71.
was shown to increase drug adherence without any 12. Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L,
increase in anxiety or stress levels in either the patients or Langan Y, et al. Combined analysis of risk factors for
their caregivers [34]. More experience is needed in this SUDEP. Epilepsia. 2011;52:1150-9.
field to understand parental perceptions and reactions. 13. Tao JX, Yung I, Lee A, Rose S, Jacobsen J, Ebersole JS.
Tonic phase of a generalized convulsive seizure is an
CONCLUSION independent predictor of postictal generalized EEG
suppression. Epilepsia. 2013;54:858-65.
SUDEP is an under-recognized but important threat in 14. Lamberts RJ, Gaitatzis A, Sander JW, Elger CE, Surges R,
patients with epilepsy. It is important to assess SUDEP Thijs RD. Postictal generalized EEG suppression: An
risk in all epilepsy patients, particularly in those with inconsistent finding in people with multiple seizures.
generalized tonic-clonic convulsions, nocturnal seizures, Neurology. 2013; 81:1252-6.
15. Skluzacek JV, Watts KP, Parsy O, Wical B, Camfield P.
as well as co-morbid developmental delay. Appropriate
Dravet syndrome and parent associations: The IDEA
antiepileptic drug therapy with stress on compliance, League experience with comorbid conditions, mortality,
early surgical referral for surgically remediable management, adaptation, and grief. Epilepsia. 2011;52:95-
epilepsies, avoiding post-seizure prone positioning, and 101.
caretaker counseling and support will go a long way in the 16. Buchanan GF. Impaired CO2-induced arousal in SIDS and
prevention of this condition. SUDEP. Trend Neurosci. 2019:42:242-50.

17. Moseley BD, Wirrell EC, Nickels K, Johnson JN, induced sudden death in a chronic SUDEP model by
Ackerman MJ, Britton J. Electrocardiographic and semichronic administration of a selective serotonin
oximetric changes during partial complex and generalized reuptake inhibitor. Epilepsy Beh. 2011;22:186-90.
seizures. Epilepsy Res. 2011;95:237-45. 27. Bateman LM, Li CS, Lin TC, Seyal M. Serotonin reuptake
18. Mukherjee S, Tripathi M, Chandra PS, Yadav R, inhibitors are associated with reduced severity of ictal
Choudhary N, Sagar R, et al. Cardiovascular autonomic hypoxemia in medically refractory partial epilepsy.
functions in well-controlled and intractable partial Epilepsia. 2010;51:2211-4.
epilepsies. Epilepsy Res. 2009;85:261-9. 28. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP.
19. Zijlmans M, Flanagan D, Gotman J. Heart rate changes and Naltrexone in the treatment of alcohol dependence. Arch
ECG abnormalities during epileptic seizures: Prevalence Gen Psych. 1992;49:876-80.
and definition of an objective clinical sign. Epilepsia. 29. Maguire MJ, Jackson CF, Marson AG, Nolan SJ.
2002;43:847-54. Treatments for the prevention of sudden unexpected death
20. Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, in epilepsy (SUDEP). Cochrane Database Syst Rev.
Bleasel A, et al. Incidence and mechanisms of cardio- 2016;7:CD011792.
respiratory arrests in epilepsy monitoring units 30. Srivastava K, Sehgal R, Konanki R, Jain R, Sharma S,
(MORTEMUS): A retrospective study. Lancet Neurol. Mittal R. Association of Child Neurology-Indian Epilepsy
2013;12:966-77. Society Consensus Document on Parental Counseling of
21. Li MCH, O’Brien TJ,Todaro M, Powell KL. Acquired Children with Epilepsy. Indian J Pediatr. 2019;86:608-16.
cardiac channelopathies in epilepsy: Evidence, mechanisms 31. Ramachandrannair R, Jack SM, Meaney BF, Ronen GM.
and clinical significance. Epilepsia. 2019:60: 1753-67. SUDEP: What do parents want to know? Epilepsy Beh.
22. Toczek MT, Carson RE, Lang L, Ma Y, Spanaki MV, Der 2013;29:560-4.
MG, et al. PET imaging of 5HT1A receptor binding in 32. Fong CY, Lim WK, Kong AN, Lua PL, Ong LC. Provision
patients with temporal lobe epilepsy. Neurology. of sudden unexpected death in epilepsy (SUDEP)
2003;60:749-56. information among Malaysian parents of children with
23. Tortella FC, Long JB, Holaday JW. Endogenous opiate epilepsy. Epilepsy Behav. 2017;75:6-12.
systems: Physiological role in the self-limitation of 33. Gayatri NA, Morrall MC, Jain V, Kashyape P, Pysden K,
seizures. Brain Res. 1985;332:174-8. Ferrie C. Parental beliefs regarding the provision and
24. Paterson DS, Trachtenberg FL, Thompson EG, Belliveau content of written sudden unexpected death in epilepsy
RA, Beggs AH, Darnall R, et al. Multiple serotonergic (SUDEP) information. Epilepsia. 2010;51:777-82.
abnormalities in sudden infant death syndrome. JAMA. 34. Radhakrishnan DM, Ramanujam B, Srivastava P, Dash D,
2006;296:254-32. Tripathi M. Effect of providing sudden unexpected death in
25. Langan Y, Nashef L, Sander JW. Case-control study of epilepsy (SUDEP) information to persons with epilepsy
SUDEP. Neurology. 2005;64;1131-3. (PWE) and their caregivers experience from a tertiary care
26. Faingold CL, Tupal S, Randall M. Prevention of seizure- hospital. Acta Neurol Scand. 2018;138:417-24.
ADVERTISEMENT

EDITORIAL COMMENTARY
Refining Clinical Triage and Management of Dengue Infection in Children:

A Timely Approach
ANITA SHET* AND KAYUR MEHTA
International Vaccine Access Center, Department of International Health,
Johns Hopkins Bloomberg School of Public Health, USA.
*ashet1@jhu.edu
T
he World Health Organization (WHO) declared without warning signs, dengue with warning signs, and
dengue infection to be one of the top ten severe dengue [5]. This classification was mainly aimed at
threats to global health in 2019. In defiance of optimizing the recognition of warning signs early in the
medical progress, dengue has achieved the disease course, thereby enhancing clinical decision
notoriety of being an infectious disease that has relent- making and disease management. Seven clinical signs
lessly increased in magnitude and geographic reach over were identified as warning signs for severe dengue, based
the past several decades. The dramatic increase in the largely on global expert consensus and supplemented by
magnitude and frequency of dengue has been attributed findings from the DENCO study, a large multicenter study
to unprecedented human population growth, unplanned in Southeast Asia and Latin American countries
urbanization and expansion of travel and globalization. conducted in 2006-2007 [6]. Severe dengue was defined
Modelling estimates indicated that there are 390 million as infection with at least one of the following: severe
dengue virus infections annually, with approximately 100 plasma leakage leading to shock or fluid accumulation,
million cases manifesting clinically, with 70% of the actual with respiratory distress, severe bleeding, or severe
burden being in Asia [1]. The vast majority of those organ impairment. However, this classification fails to
infected are children. The global suffering caused by this identify the precise parameters that define these signs,
vector-borne virus, while eclipsed in magnitude by the leading to a great deal of heterogeneity in the use of this
current SARS-CoV-2 pandemic, has not abated in parts of system, a problem well-described in a recent systematic
the world where dengue is endemic. Unexpected surges review [7]. The sensitivity of this classification to identify
of dengue case counts have been reported this year in severe dengue has ranged between 59-98%, and speci-
many places, and this phenomenon is likely to pose ficity between 41-99% [8]. It has been argued that the
serious challenges to already overburdened healthcare severe dengue entity as defined by the 2009 classification
systems across the world [2]. As dengue and COVID-19 represents a mix of end-stage manifestations involving
share several clinical and laboratory features, cases of various clinical pathways, potentially including comorbi-
misdiagnosis, serological cross-reactivity and co-infec- dities and other iatrogenic factors [9]. Most importantly,
tion have been described, further complicating manage- the 2009 classification fails to identify standard, quanti-
ment [3]. It is therefore especially critical, now more than fiable clinical endpoints which are needed to ensure
ever, that the classification systems for dengue ensure reproducibility and comparability of research findings,
validity and reproducibility for both clinical management thereby limiting its application in research studies, such
and research studies. as studies aiming to study the safety, efficacy and
effectiveness of a dengue vaccine or therapeutic agent.
The traditional WHO classification for dengue,
implemented from 1974 onwards based on experience with An expert working group assembled in 2015 used the
pediatric dengue in Thailand, was revised in 1997, and Delphi method of interactive consensus-driven guideline
classified dengue disease as dengue fever, dengue formulation to derive dengue disease severity endpoints
hemorrhagic fever, and dengue shock syndrome. This for use in clinical trials of dengue therapeutics and
classification, despite being evidence-based, was vaccine research [10]. Consensus was reached on most
critiqued for underestimating the clinical burden of the parameters including, moderate and severe plasma
infection, and for poorly distinguishing the milder and leakage, bleeding, and organ involvement (liver, heart and
more severe forms of dengue [4]. The revised 2009 neurologic disease) [10]. By applying these new
classification that eventually replaced the previous definitions on the 2006 DENCO dataset to identify
system describes the following categories: dengue measurable clinical endpoints, experts concluded that

EDITORIAL
severe vascular leakage is an entity distinct from other Funding: None; Competing interests: None stated.
severe manifestations such as bleeding or organ REFERENCES
dysfunction, and may be used as a reliable endpoint for
intervention research [11]. While definitions for mild and 1. Bhatt S, Gething PW, Brady OJ, et al. The global
severe dengue disease were established, a clear definition distribution and burden of dengue. Nature. 2013;496:
of ‘moderate’ disease severity was identified as a need for 504-07.
2. Lorenz C, Azevedo TS, Chiaravalloti-Neto F. COVID-19
conducting cross-validated research. It is clear that
and dengue fever: A dangerous combination for the health
further prospective studies to validate standardized clini- system in Brazil. Travel Med Infect Dis. 2020;35:101659.
cal endpoints for dengue disease of differing severity 3. Harapan H, Ryan M, Yohan B, et al. Covid-19 and dengue:
categories are important for filling these gaps. Double punches for dengue-endemic countries in Asia. Rev
Med Virol. 2020:e2161.
Sreenivasan, et al. [12] are to be commended for
4. Phuong CX, Nhan NT, Kneen R, et al. Clinical diagnosis and
embarking on the exceedingly difficult task of determining assessment of severity of confirmed dengue infections in
how the warning signs described in the 2009 WHO Vietnamese children: Is the world health organization
classification of dengue can predict time for disease classification system helpful? Am J Trop Med Hyg. 2004;
progression from moderate to severe dengue among 70:172-79.
children. They conclude that vascular leakage as 5. World Health Organization: Dengue: Guidelines for
manifested by clinical fluid accumulation, and hemo- Diagnosis, Treatment, Prevention and Control (2nd edn).
concentration measured by hematocrit ≥40%, are impor- WHO, 1997. Accessed September 21, 2020. Available at:
tant manifestations that are predictive of a shortened time https://www.who.int/tdr/ publications/documents/dengue-
diagnosis.pdf 2009
towards progressing to severe dengue [12]. Their
6. Alexander N, Balmaseda A, Coelho IC, et al. Multicentre
findings imply the need for heightened surveillance and prospective study on dengue classification in four South-
supple-ment other studies of clinical endpoints in east Asian and three Latin American countries. Trop Med
dengue. The hallmark of severe dengue, particularly in the Intern Health. 2011;16:936-48.
younger age group, is vascular permeability leading to 7. Morra ME, Altibi AMA, Iqtadar S, et al. Definitions for
plasma leakage, and subsequent circulatory shock and its warning signs and signs of severe dengue according to the
consequences, which can be life threatening. The authors WHO 2009 classification: Systematic review of literature.
highlight the importance of other clinical manifestations Rev Med Virol. 2018; 28:e1979.
such as persistent vomiting and mucosal bleeding in 8. Horstick O, Jaenisch T, Martinez E, et al. Comparing the
usefulness of the 1997 and 2009 WHO dengue case
predicting time to severe disease progression. Early
classification: a systematic literature review. Am J Trop
recognition and close monitoring of these clinical Med Hyg. 2014; 91:621-34.
manifestations, along with timely institution of 9. Halstead SB. Controversies in dengue pathogenesis.
appropriate management can spell the difference between Paediatr Int Child Health. 2012;32:5-9.
therapeutic success and failure among children with 10. Tomashek KM, Wills B, See Lum LC, et al. Development of
dengue infection. In the current pandemic era, while standard clinical endpoints for use in dengue interventional
resources are diverted to address the devastating effects trials. PLoS Negl Trop Dis. 2018;12:e0006497.
of COVID-19, the toll of ongoing infections such as 11. Rosenberger KD, Alexander N, Martinez E, et al. Severe
dengue must not be forgotten. The overlapping dengue categories as research endpoints-Results from a
prospective observational study in hospitalised dengue
challenges of dengue and COVID-19 prompt an urgent
patients. PLoS Negl Trop Dis. 2020;14:e0008076.
call to action for continued disease surveillance, ongoing 12. Sreenivasan P, Geetha S, Santhosh Kumar A. WHO 2009
attention to clinical and environmental management, and warning signs as predictors of time taken for progression to
increased focus on research needs. severe dengue in children. Indian Pediatr. 2020;57:899-903.

EDITORIAL COMMENTARY
Identifying India’s Dual Nutrition Burden: Role of Body Mass Index

Quick Screening Tool
SANGITA YADAV
Department of Pediatrics, Maulana Azad Medical College and L N Hospital, University of Delhi, New Delhi 110002, India.
drsangeetayadav18@gmail.com
A
dual nutrition burden of undernutrition with difficult to interpret and compare the global or national
rise in childhood obesity was recognized in prevalence rates. For children and adolescents, over-
India in the latter decade of the twentieth weight and obesity are usually defined using age and
century [1].Yes, the pendulum has swung gender specific nomograms of BMI. The Indian Academy
from the era of undernutrition from 1960s-80s to the era of Pediatrics recommends the revised growth charts for
of plenty, leading to over-nutrition from late 90s till the height, weight and BMI for assessment of growth of
present. The healthcare systems are now focusing on the Indian children aged 5-18 year. Overweight and obesity
burden of obesity in childhood because of its long term have been defined using adult equivalent of 23 kg/m2 and
consequences of non-communicable diseases in 27 kg/m2 cut-offs presented in BMI charts in children from
adulthood [2]. However, surveillance for undernutrition 5-18 years [7]. Higher prevalence of obesity and
is imperative as part of the life cycle approach to ensure overweight was reported with IAP 2015 reference than
optimum health at birth and later in life. The Prime IOTF and WHO 2007 standards in the age group of 8-18
Minister’s Overarching Scheme for Holistic Nourishment years, with good agreement [8].
(POSHAN) Abhiyaan, a multi-ministerial convergence
With the need to identify over nutrition early, it is
mission, was initiated in 2018 by the Government of India to
important to calculate and plot BMI at least once a year in
ensure adequate nutrition of pregnant women and
all children and adolescents, and identify weight patterns
lactating mothers and holistic development of children,
relative to linear growth. The use of charts helps track
with a vision to attain malnutrition-free India by 2022 [3] .
BMI to give guidance. Monitoring of BMI is; however,
Body mass index (BMI) is currently the best simple often overlooked in routine clinical practice unless the
available anthropometric estimate of fatness for public issue is recognized by parents, which may be rather late at
health purposes, proposed first by Cole, et al. [4] in times. Many parents would need an interpretation of their
children in 1979, which adjusts weight for both height child’s BMI and assessment of their child’s health risks.
and age. The validity of anthropometric data as a proxy Defining one or more cut-off points on the BMI chart
for body fat identifies children at risk and correlates determines the advice to be communicated to the parents
better with measures of body fat mass [4]. The at a stage when interventions might be easier.
International Obesity Taskforce (IOTF) pooled data from
The ‘ELIZ health path for adolescents and adults
six international BMI references to define the centile cut
(EHPA)’ novel growth assessment chart was designed to
offs at 18 years of age to match the adult cut offs of 25
plot the height on the X axis and weight on the Y axis and
kg/m2 and 30 kg/m2 for overweight and obesity. However,
then read the BMI from the right margin in accordance
studies conducted in India showed the IOTF reference
with the International Obesity Task Force (IOTF)
classified participants as having a lower weight and
recommendations for the various age groups [9]. The
concluded that IOTF criteria were not suitable for Indian
lower and the higher cut-off indicators on this chart were
and South Asian children [5]. Thus, lower BMI cut-offs of
found appropriate for preliminary screening of a large
23 kg/m2 and 25 kg/m2 have been suggested by the World
number of children and adolescents in the community
Health Organization (WHO) and IOTF for Asian Indian
setting [9,10].
adults for overweight and obesity, respectively but these
are not applicable for children and adolescents [6]. Over In this issue Khadilkar, et al. [11] report on the
the years, there has been a lack of consensus on the development of a graphic tool for the BMI cut offs,
various cut-points or definitions used to classify obesity without need for calculating BMI, for screening from 8
and overweight in children and adolescents. This makes it years onwards for underweight, overweight and obesity,

EDITORIAL
which complements the existing IAP 2015 charts. They provide national and local data that would inform the
validated the tool using de-identified data on children planning and evaluation of intervention programs. BMI
from school health surveys and found that the BMI tool can be an effective screening test for undernutrition;
had a sensitivity of 100% for both boys and girls with a however, the statistical cut-off points are inherently
specificity of 88.9% and 82.4% for boys and girls, arbitrary and must be followed up by a more detailed
respectively for underweight. The sensitivity and evaluation to assess the risks and plan intervention.
specificity was 95.7% and 85.7% for boys, and 95.7%
Funding: None; Competing interest: None stated.
and 89.7% for girls, respectively for detection of
overweight and obesity. Thus, the tool demonstrated high REFERENCES
sensitivity and specificity for screening children for
1. Mathur P, Pillai R. Overnutrition: Current scenario and
underweight, overweight and obesity against IAP BMI
combat strategies. Indian J Med Res. 2019;149:695-705
charts. They also observed that the tool may wrongly 2. India State-Level Disease Burden Initiative Malnutrition
categorize children at extreme ends of height for age. Collaborators. The burden of child and maternal
However, larger studies with a bigger sample size are malnutrition and trends in its indicators in the states of
required for validation and generalization of the tool. The India: the Global Burden of Disease Study 1990-2017
tool is gender-specific and is based on height and weight, [published correction appears in Lancet Child Adolesc
which eliminates the need for calculation of BMI, and Health. 2019 Sep 30]. Lancet Child Adolesc Health.
may help pediatricians to rapidly screen for any changes 2019;3:855-70.
in BMI in a busy clinical practice. 3. NITI Aayog. POSHAN Abhiyaan. Available at URL:
https://niti.gov.in/poshan-abhiyaan. Accessed September
Efforts to decrease the existing nutritional scenario of 12, 2020.
dual burden of undernutrition alongside emerging over 4. Hall DMB, ColeTJ. What use is the BMI? Arch Dis Child
nutrition should be a top priority. The present narrative 2006; 91:283-6.
shows that overweight and obesity rates in children and 5. Ranjani H, MehreenTS, Pradeepa R, et al. Epidemiology of
childhood overweight & obesity in India: A systematic
adolescents are increasing among the higher socio-
review. Indian J Med Res. 2016;143:160-74.
economic groups and in the lower income groups where 6. Cole TJ, Lobstein T. Extended international (IOTF) body
underweight still remains a major concern. No country mass index cut-offs for thinness, overweight and
can aim to attain economic and social development goals obesity. Pediatr Obes. 2012;7:284-94.
without addressing the issue of malnutrition. This 7. Indian Academy of Pediatrics Growth Charts Committee.
suggests the need for a balanced and sensitive approach Khadilkar V, Yadav S, Agrawal KK, et al. Revised IAP
addressing economic and nutrition transitions to Growth Charts for Height, Weight and Body Mass Index
effectively tackle this double burden paradox in India. for 5- to 18-Year-Old Indian Children. Indian Pediatr.
Since the comorbidities of undernutrition, low birth 2015;52:47-55.
8. Chudasama RK, Eshwar T, Eshwar ST, Thakrar D.
weight, and overweight/obesity with associated non-
Prevalence of Obesity and Overweight Among School
communicable diseases co-exist in India, it is important Children Aged 8-18 Years in Rajkot, Gujarat. Indian
to integrate nutritional concerns in developmental Pediatr. 2016;53:743-4.
policies. 9. Elizabeth KE. A novel growth assessment chart for
adolescents. Indian Pediatr. 2001; 38:1061-4.
The key to long-term solutions lies in prevention with
10. Elizabeth KE, Muraleedharan M. Three-in-one weight,
a proactive approach.BMI performs moderately well as a height and body mass index charts for children and adults. J
proxy for nutritional indicators and is the best available Trop Pediatr. 2003;49: 224-7.
tool for monitoring progress in the campaign for 11. Khadilkar V, Lohiya N, Chiplonkar S, Khadilkar A. Body
identifying malnutrition in India. A robust quality assured mass index quick screening tool for IAP 2015 growth
anonymized data collection and analysis system can charts. Indian Pediatr. 2020;57:904-06.

RESEARCH PAPER
WHO 2009 Warning Signs as Predictors of Time Taken for Progression to

Severe Dengue in Children
PRIYA SREENIVASAN,1,2 S GEETHA1,2 AND A SANTHOSH KUMAR1
From Department of 1Pediatrics, and 2Clinical Epidemiology Resource and Training Centre (CERTC), Government Medical
College, Thiruvananthapuram, Kerala.
Correspondence to: Dr Priya Sreenivasan, Associate Professor of Pediatrics, Government Medical College, Thiruvananthapuram,
Kerala, India. priyavineed16@gmail.com
Received: August 14, 2019; Initial reviews: November 14, 2019; Accepted: June 10, 2020.
Objective: To identify WHO 2009 warning signs that can predict signs: abdominal pain, lethargy, persistent vomiting, mucosal
time taken for progression to severe dengue in a pediatric bleed, clinical fluid accumulation, hepatomegaly >2 cm,
population. hematocrit ≥0.40 and platelet count <100x109/L.
Design: Prospective analytical study over 1 year and 2 months. Results: Among 350 children followed up completely till
Setting: Tertiary care center. discharge/death, 90 developed severe dengue (event) while 260
did not (censored). Median age of study population was 7.75 y.
Participants: 350 children aged 1 mo-12 y with serologically Clinical fluid accumulation [(P=0.002, Hazard Ratio (HR) 2.19,
confirmed dengue without co-morbidities/co-infections; conse- 95% CI 1.33-3.60)] and hematocrit ≥0.40 [(P=0.009, HR (95%CI)
cutive sampling. 1.715, (1.13-2.60)] were significant in univariate analysis. Final
Procedure: At admission, clinical and laboratory details were multivariate model includes clinical fluid accumulation [(P=0.02,
noted. Disease progression, time of onset of each warning sign, HR (95%CI) 1.89, (1.116-3.202)], hematocrit ≥0.40 (P=0.07),
hematocrit, and platelet counts were recorded daily till discharge/ mucosal bleed (P=0.56) and persistent vomiting (P=0.32).
death. If progressing to severe dengue, its time of onset was Conclusion: WHO warning signs that predict time taken for
noted. Time to event analysis with Log Rank test, Kaplan Meier progression to severe dengue in children include clinical fluid
plots and Cox Proportional Hazards Model was done. accumulation, hematocrit ≥0.40, persistent vomiting and mucosal
Outcome Measures: Primary outcome was time interval from bleed. Study results have implications in policy making and
onset of first warning sign to onset of severe dengue (defined as practice guidelines to triage children attending a health care
per WHO 2009 guidelines). Predictors were WHO 2009 warning facility with or without warning signs.
Keywords: Hematocrit, Management, Outcome, Prognosis.
D
engue is a globally prevalent arboviral A prognostic prediction model using seven WHO
infection with high morbidity and mortality in warning signs to determine severe dengue in children has
India [1]. Kerala reported 19,912 dengue cases been published earlier [6]. Dynamicity of illness can be
with 37 deaths in 2017 [2]. Dengue is dynamic captured by taking into consideration the time to time
with febrile phase, critical phase (appearance of warning variations in clinical and laboratory variables [7]. The
signs at/around defervescence mark onset of capillary present study aimed to identify warning signs which can
leak) and convalescent phase [3]. Seven warning signs predict time taken for progression to severe dengue in
viz. abdominal pain, lethargy, mucosal bleed, persistent children admitted to a tertiary care center.
vomiting, clinical fluid accumulation, hepatomegaly >2 cm
and rising hematocrit with a concurrent fall in platelet Editorial Commentary: Pages 895-96.
count below 100×109/L are evidence-based signs
METHODS
selected by the World Health Organization (WHO) [3,4].
Potentially lethal severe dengue can manifest as shock, This prospective study was done in a tertiary care setting
severe bleed or severe organ impairment in the critical over one year and two months (2015-16). All
phase or in the febrile phase without preceding warning serologically confirmed dengue patients (either NS1Ag
signs [3]. Close monitoring and timely initiation of positivity, if admitted within first 5 days of fever, or IgM
intravenous fluids in the presence of any warning signs positivity, if after 5 days of fever) between 1 mo-12 y
remain the only effective treatment modality in dengue without co-morbidities or co-infections were enrolled by
[3]. Severe dengue manifests as mostly shock in children consecutive sampling. At admission, baseline history,
and as severe bleeding and organ impairment in adults [5]. clinical examination and laboratory investigations (total

SREENIVASAN, ET AL. WHO WARNING SIGNS FOR SEVERE DENGUE
count, hematocrit, platelet counts, liver and renal function had co-morbidities, 8 had co-infections, 7 did not have
tests) were recorded. Close monitoring was done to note any warning signs and 2 had onset of severe dengue
the time of onset of warning signs and severe dengue if before onset of the first warning signs. They were
any and need for administration of intravenous fluids till excluded and among remaining 350, 90 (25.7%)
discharge or death. Daily examination for clinical fluid progressed to severe dengue (event); 4 patients with
accumulation, hepatomegaly, hematocrit and platelet severe dengue died. Remained 260 children (74.3%) did
count were done in all patients. In case of rising not progress to severe dengue and were considered ‘right
hematocrit, intravenous fluids were started, titrated (as censored’ in time to event analysis.
per WHO 2012 guidelines) and hematocrit repeated. In
Median (IQR) age of study population was 7.75 (4.75,
patients with clinical worsening, 4 hourly hematocrit, 12
10.25) year. There were 21 infants and 188 (53.7%) were
hourly platelet count, and 2 hourly clinical examinations
males. Proportion of children who progressed to severe
were done, as per hospital protocol. Ethical clearance
dengue as evidenced by compensated shock, decompen-
was obtained from Institutional Review Board.
sated shock, respiratory distress, severe bleed and
Primary outcome was time duration from onset of first severe organ impairment as per WHO definitions were
warning signs to onset of severe dengue defined as 23.1%, 16%, 4.6%, 1.4% and 4.6%, respectively. Median
attainment of either severe plasma leak leading to shock (IQR) day of admission to our center was on day 5 (4, 6).
and/or fluid accumulation with respiratory distress, severe 154 subjects were NS1Ag positive, 163 were IgM positive
bleed or severe organ impairment [3]. Seven WHO, 2009 and 33 were both positive; 22.1%, 29.4% and 24.2%
warning signs (dichotomized as yes/no) were: abdo-minal progressed to SD respectively. Median (IQR) length of
pain (severe enough to warrant medical attention), lethargy follow-up was 5 (4, 6) days (Table I).
(without altered sensorium), persistent vomiting (≥2 Log rank test was applied to the data and Kaplan
episodes of vomiting that amounts to fatigue or requires Meier curves were drawn to compare between
intravenous fluids), mucosal bleed (any bleed from groups with and without each warning sign (Table II,
gastrointestinal/genitourinary mucosa, nose, conjunctiva), Fig. 2a, 2b). Final model includes all warning signs with
clinical fluid accumulation (either pleural effusion not P<0.2 in univariate analysis (clinical fluid accumulation,
severe enough to cause respiratory distress as evidenced mucosal bleed, persistent vomiting and hematocrit ≥0.40)
by reduced intensity of breath sounds on auscultation of (Table III).
axillary areas or ascites as evidenced by shifting dullness),
hepatomegaly >2 cm, hematocrit ≥0.40 (cut-off decided by Receipt of intravenous fluids could confound time
constructing a receiver operating characteristic curve) and taken for progression to severe dengue, but statistical
a fall in platelet count <100×109/L [6]. significance was not obtained in univariate analysis with
time to event as outcome.
Sample size for number of events in each group in
survival analysis was calculated where in δ is natural DISCUSSION
logarithm of the expected ratio of hazards at a given time The study shows that clinical fluid accumulation,
[8]. For a two-tailed test (α 0.05 and β 0.2), by keeping δ hematocrit ≥0.40, mucosal bleed and persistent vomiting
arbitrarily as 1.6, number of events (severe dengue) predict time taken for progression to severe dengue.
needed in each group was calculated as 71; by keeping δ Earlier, authors developed a prognostic prediction model
arbitrarily as 2, events needed in each group was 33. to determine severe dengue in children that included
Statistical analyses: Descriptive statistics and time to clinical fluid accumulation hematocrit ≥0.40 with platelet
event data analysis were performed with SPSS version count <100×109/L and persistent vomiting [6].
20. Univariate analysis was done for each warning signs In the present study, clinical fluid accumulation
with time taken for progression to severe dengue as appeared late with a median time of onset of 144 h from
outcome; Kaplan Meier graphs were drawn. Predictor onset of fever. Moreover, median time of onset of severe
significance for inclusion in the multivariate model was dengue is only 2h from onset of clinical fluid
predetermined (α 20%). Cox proportional hazards model accumulation. In most situations, authors were the first to
was checked by looking for parallel lines with and identify clinical fluid accumulation; being a tertiary
without each predictor in scatter plots with log time along setting, exact time of onset of clinical fluid accumulation
X-axis and -log [-log (Survival function)] along Y-axis [9]. could not be delineated. In our study, hematocrit
RESULTS appeared late probably because the investigation was not
sent before admission to our center. Even then, median
Among 386 serologically confirmed dengue patients, 9 time of onset of severe dengue was 5h after onset of

Table I Time of Onset of Warning Sign and Time of Onset of Severe Dengue (N=350)
Characteristic Abdominal Persistent Lethargy Hepatomegaly Clinical fluid Mucosal Platelet count Hematocrit
pain vomiting >2cm accumulation bleed <100×109/L ≥ 0.40
Total with WS* 217 99 327 162 64 72 284 123
(62) (28.2) (93.4) (46.2) (18.2) (20.5) (81.1) (35.1)
Time of onset 72 24 6 144 144 132 120 144
of WS (h) (6,120) (6,120) (6,72) (120,168) (144,168) (96,162) (120,144) (120,168)
Total with WS 211 98 326 143 46 56 270 113
before event* (60.2) (28) (93.1) (40.8) (13.1) (16) (77.1) (32.2 )
Total events* 58 35 86 36 26 21 69 42
(16.5) (10) (24.5) (10.2) (7.4) (6) (19.7) (12)
Time to onset of 48 120 120 2 2 24 18 5
event after WS (h) (6,120) (24,144) (48,144) (2,3) (1,4) (4,48) (2,24) (2,24)
Values in median (IQR) except *n(%); WS-warning sign.
Table II Children With Each Warning Sign Who Progressed to Severe Dengue (Event) and Event Free Time
Warning sign Total Events Survival Time P value Crude OR
n= 90 (95% CI), min (95% CI)
Yes 211 58 (153) 359.7 (328.98-390.43) 0.87 1.04
No 139 32 (107) 324.1 (291.19-357.02) (0.67-1.59)
Lethargy
Yes 326 86 (240) 362.5 (337.46-387.60) 0.69 1.26
No 24 4 (20) 167.2 (141.90-192.59) (0.39-3.99)
Persistent vomiting
Yes 98 35 (63) 276.4 (242.73-310.04) 0.13 1.38
No 252 55 (197) 384.1 (356.53-411.64) (0.90-2.10)
Clinical fluid accumulation
Yes 46 26 (20) 178.3 (146.04-210.48) 0.002 2.19
No 304 64 (240) 379.1 (353.64-404.59) (1.33-3.59)
Hepatomegaly
Yes 143 36 (107) 363.8 (339.18-388.35) 0.81 1.01
No 207 54 (153) 370.7 (338.81-402.67) (0.69-1.59)
Mucosal bleed
Yes 56 21 (35) 204.8 (177.67-231.89) 0.14 1.45
No 294 69 (225) 370.3 (342.62-398.01) (0.89-2.36)
Hematocrit ≥0.40
Yes 113 42 (71) 265.5 (232.60-298.35) 0.009 1.71
No 237 48 (189) 392.3 (364.75-419.91) (1.13-2.59)
Platlet count <100x109/L
Yes 270 69 (201) 314.6 (291.83-337.30) 0.97 1.01
No 80 21 (59) 382.0 (333.96-430.14) (0.61-1.66)
hematocrit ≥0.40. This time gap is clinically valuable for do exist for which stratum specific analysis might have
initiating close monitoring, intensive care and early been helpful. Administration of intravenous fluids was
referral if needed. This makes hematocrit ≥0.40 a clinically thought of as a potential confounder but statistical
relevant warning signs. Kaplan Meier curves drawn for significance was not obtained in univariate analysis.
clinical fluid accumulation and hematocrit ≥0.40 as Possibility of unknown confounders should be thought
predictors intersect at some points. Hence confounders of in this context.

Fig. 1 Kaplan Meier Curve showing survival function over time Fig. 2 Kaplan Meier curve showing survival function over time in
in the absence (upper line) and presence (lower line) of CFA as the absence (upper line) and presence (lower line) of HCT >0.40
predictor. as predictor.
Mucosal bleed and persistent vomiting are two dengue and hence may influence time to event. Detailed
objective symptoms, time of onset of which the caretaker investigations to delineate infection as primary or secon-
may easily notice. An added advantage of persistent dary were not done in our study. Our study period included
vomiting is its early appearance in the disease course. A two dengue seasons, but only 90 patients progressed to
sufficient time gap between time of onset of persistent severe dengue which was below the estimated sample size.
vomiting and time of onset of severe dengue was also
A previous survival analysis assessed survival of
demonstrated in our study. Due to these clinical reasons,
adult dengue patients in relation to the severity of liver
mucosal bleed and persistent vomiting were included in
dysfunction [10]. Survival analysis of a pediatric popu-
the final model.
lation has identified that acute renal failure adversely
In our tertiary care setting, some patients had onset of affects survival rates [11]. In these studies, event was
warning signs even before admission to our hospital. To mortality whereas in our study, event severe dengue.
minimize this recall bias, details from referral letters were Lam, et al. [7] have found that prediction models with
collected and telephonic conversations with referring serial daily platelet counts demonstrated better ability to
doctor were done wherever needed. Though technically, discriminate patients who developed shock than models
260 patients were right censored, all were completely based on enrolment information only [7]. They concluded
followed up till recovery as evidenced by fever free period that development of dynamic prediction models that
of 48 hours, disappearance of clinical warning signs, rising incorporate signs, symptoms and daily laboratory
trend of platelet counts and a normal hematocrit. Secondary measurements could improve dengue shock prediction.
infection is a strong risk factor of progression to severe In our study, all seven WHO warning signs have been
included for the purpose of prediction.
Table III Cox Proportional Hazards Model With Selected Our results may be generalized to children attending a
Warning Signs health care facility with dengue. As India is hyper-
Warning Model including CFA, Model including CFA, endemic for dengue, the study results have implications
signs HCT ≥0.40, PV HCT≥0.40 in policy making and practice guidelines, especially to
and MB and MB triage children attending a health care facility with or
HR (95% CI) P value HR (95% CI) P value without warning signs. To conclude, WHO warning signs
that can predict time taken for progression to severe
CFA 1.89 (1.11-3.20) 0.02 1.85 (1.09-3.12) 0.02
dengue in children include clinical fluid accumulation,
Hct ≥0.40 1.49 (0.96-2.29) 0.07 1.54 (1.00-2.35) 0.05 hematocrit ≥0.40, persistent vomiting and mucosal bleed.
MB 1.17 (0.69-1.97) 0.56 1.25 (0.76-2.07) 0.38
Acknowledgements: Dr Sasikala K, Director, CERTC, Govern-
PV 1.25 (0.80-1.95) 0.32 - -
ment Medical College, Thiruvananthapuram for the conduct of
CFA: Clinical fluid accumulation; Hct: Hematocrit; PV: Persistent this study.
vomiting; MB: Mucosal bleed; HR: Hazard ratio. Ethics clearance: Institutional Review Board, Government

WHAT IS ALREADY KNOWN?

• Among seven warning signs suggested by WHO in 2009, clinical fluid accumulation, rising hematocrit
9
concurrent with rapid fall in platelet count <100x10 /L and persistent vomiting predict severe dengue in children.
WHAT THIS STUDY ADDS?
• WHO warning signs that predict time taken for progression to severe dengue in children include clinical fluid
accumulation, hematocrit ≥0.40, persistent vomiting and mucosal bleed.
Medical College, Thiruvananthapuram; No. 06/62/2015/MCT, 5. DinhThe T, Le Thi Thu T, Nguyen Minh D, Tran Van N,
dated December 09, 2015. Tran Tinh H, Nguyen Van Vinh C, et al. Clinical features of
Contribution: PS: conceived the idea, designed the metho- Dengue in a large Vietnamese cohort: Intrinsically lower
dology, collected and analysed data and prepared the manuscript; platelet counts and greater risk for bleeding in adults than
GS: guided conduct of the study, critically reviewed the children. PLoSNegl Trop Dis. 2012;6:e1679.
manuscript; SKA: elaborated the concept, interpreted the results, 6. Sreenivasan P, S Geetha, K Sasikala. Development of a
critically reviewed the manuscript and approved final version to prognostic prediction model to determine severe dengue in
be published. All authors approved the final version of manu- children. Indian J Pediatr. 2018;85:433-39.
script, and are accountable for all aspects related to the study. 7. Lam PK, Ngoc TV, Thu Thuy TT, Hong Van NT, NhuThuy
Funding: None; Competing interests: None stated. TT, Hoai Tam DT, et al. The value of daily platelet counts
for predicting dengue shock syndrome: Results from a
REFERENCES
prospective observational study of 2301 Vietnamese
1. World Health Organization. Dengue and Severe Dengue. children with dengue. PLoS Negl Trop Dis. 2017;11:
Available from https://www.who.int/news-room/fact- e0005498.
sheets/detail/dengue-and-severe-dengue/. Accessed July 8. Norman GR and Streiner DL. Nonparametric statistics.
25, 2019. Life Table (Survival Analysis). In: Norman GR and
2. National Vector Borne Disease Control Programme. Streiner DL, editors. Biostatistics. The bare essentials.
Dengue. Dengue cases and deaths in the country since Ontario: B.C Decker Inc; 1998. P.182-94.
2010. Available from https://www.nvbdcp.gov.in/den- 9. Bradburn MJ, Clark TG, Love SB and Altman DG.
cd.html/. Accessed July 25, 2019. Survival analysis Part III: Multivariate data analysis-
3. World Health Organization. Dengue Guidelines for choosing a model and assessing its adequacy and fit. Br J of
diagnosis, treatment, prevention and control: New edition Cancer. 2003;89:605-11.
2009. Available from: https://www.who.int/rpc/guidelines/ 10. Hanif A, Butt A, Ahmed A, Sajid MR, Ashraf T, Nawaz
9789241547871/en/. Accessed July 25, 2019. AA. Survival analysis of Dengue patients in relation to
4. Alexander N, Balmaseda A, Coelho ICB, Dimaano E, Hien severity of liver dysfunction in Pakistan. Adv Biolog Res.
TT, Hung NT, et al. Multicentre prospective study on 2015;9:91-94.
dengue classification in four South-east Asian and three 11. Basu B, Roy B. Acute renal failure adversely affects
Latin American countries. Trop Med Inter Health. 2011; survival in pediatric Dengue infection. Indian J Crit Care
16:936-48. Med. 2018;22:30-33.

RESEARCH PAPER
Body Mass Index Quick Screening Tool for Indian Academy of Pediatrics
2015 Growth Charts
VAMAN KHADILKAR, NIKHIL LOHIYA, SHASHI CHIPLONKAR AND ANURADHA KHADILKAR
From Department of Growth and Pediatric Endocrine, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital,
Pune, Maharashtra, India.
Correspondence to: Dr Anuradha Objective: To develop gender-specific graphic tool in which BMI cut offs can be read from
Khadilkar, Hirabai Cowasji Jehangir height and weight, without need for calculating BMI and to validate the tool against Indian
Medical Research Institute, Jehangir Academy of Pediatrics (IAP) 2015 BMI charts. Methods: Validation of tool was performed
using de-identified data on children from school health surveys. Results: For detection of
Hospital, Pune, Maharasthra, India.
overweight and obesity, the BMI tool had sensitivity of 95.7% and specificity of 85.7% for
anuradhavkhadilkar@gmail.com boys, and 95.7% and 89.7% for girls, respectively. For underweight, sensitivity of 100% for
Submitted: April 25, 2019; boys and girls, and specificity of 88.9% for boys and 82.4% for girls was observed.
Initial review: July 29, 2019; Conclusion: We present a graphic BMI tool for screening for underweight, overweight and
Accepted: April 7, 2020. obesity, which complements the existing IAP charts.
Keywords: Diagnosis, Growth chart, Obesity, Overweight, Underweight.
Published online: June 12, 2020; PII: S097475591600197
I
n recent times, while undernutrition is common in value of height, weight and cut-offs for underweight,
India [1], childhood obesity is an important health overweight and obesity were used from the IAP charts [5]
problem in urban areas, and seen commonly in older to design the tool. Ethics approval for the study was
children and adolescents than younger children [2]. obtained from the institutional ethics committee. The
Early recognition of obesity is important to prevent height range for boys and girls for the age group of 8-18
adverse health consequences in adulthood such as years was plotted on the X-axis. Based on the BMI cut off
hypertension and type 2 diabetes [3]. Further, under- value for that particular age the corresponding weight to a
nutrition during adolescence can potentially retard adole- particular height was calculated and plotted on the
scent growth spurt [4]. Indian Academy of Pediatrics secondary Y-axis (Microsoft Excel 2015). Thus, height
(IAP) Guidelines provide body mass index (BMI) charts was plotted on the X-axis, weight on the Y-axis and three
for Indian children to screen for under or over-nutrition
[5]. BMI needs to be computed and then plotted on a Editorial Commentary: Pages 897-98.
growth chart. However, in a busy pediatric out-patient
clinic, calculating BMI is time consuming and is often
lines viz, for underweight, overweight and obesity were
omitted [6]. BMI may not be plotted and hence over-
constructed on secondary Y-axis. The meeting point of
weight and underweight may be missed. Thus, there is a
the two lines gives the BMI. Depending on where the
need to create a screening tool based on height and
BMI point lies, child may be classified as being, obese,
weight that eliminates need for BMI calculation and helps
overweight, normal weight or underweight. If plotted
pediatricians rapidly screen for overweight, obesity and
reading falls below lowest line the child is underweight, if
underweight. The objective of present study was to
it is between underweight and overweight lines, the child
develop a gender-specific graphic tool in which BMI cut
has a BMI within reference range, if the reading falls
offs can be read from height on X-axis and weight on
between overweight and obese lines the child is over-
Y-axis, without the need to calculate BMI.
weight, and if above obese line, the child is considered
METHODS obese. Separate tools were created for both genders.
The health-related risks of obesity such as metabolic Sample size was calculated using external prognostic
syndrome are more common after 10 years of age or at the modeling [10] and was recommended to be more than 200.
onset of puberty and likewise recommendations for The tool was validated on de-identified data from a health
screening for metabolic syndrome [7-9]. We therefore survey [11]. Data were distributed over BMI categories as
designed the BMI tool for use from 8 years. The mean per the IAP charts into underweight, within reference

KHADILKAR, ET AL. BMI QUICK SCREENING TOOL
range, overweight and obese, and used to test sensitivity In a study where questionnaires were sent to
and specificity of BMI tool. Data on height and weight Ministries of Health of 202 countries, authors found that
from validation data set were plotted on BMI tool and growth charts were mainly used for children from 0-5
simultaneously on the IAP BMI charts. The number of years, and covered birth to adolescence in only 29% [12].
children classified as underweight, within reference More than half of the countries, including 18 Asian
range, overweight and obese by the tool and IAP charts countries, used weight for age charts instead of BMI
was noted. Sensitivity and specificity of the tool against charts [17]. In a questionnaire-based study to assess
IAP charts was computed (SPSS 25). usage of growth charts, over two-third of doctors
reported a positive attitude towards monitoring of
RESULTS
growth; how-ever, perception of high workload was
Data on 221 (112 boys) children age 8-18 years were used. associated with lower usage of growth charts [8]. There
The gender-wise BMI screening tools are illustrated in are fewer preventive visits to hospitals as children get
Fig. 1 and 2. older [13]. These reports thus underline the importance of
devising simple graphic tools to assess nutritional status
For detection of overweight and obesity in
for use in busy clinical settings.
comparison with IAP charts, sensitivity was 95.7% for
both boys and girls, whereas specificity was 85.7% for A similar unisex chart was proposed by Elizabeth,
girls and 89.7% for boys. For detection of underweight, et al. [14] in 2001 based on the International Obesity Task
sensitivity was 100% for both genders and specificity Force cut-offs [15], which may not be appropriate for
was 88.9% for boys and 82.4% for girls. Indian children at present. Unisex charts may not be
appropriate as girls stop growing earlier than boys. The
DISCUSSION
tool designed in the current study may be used in con-
We have presented a graphic tool based on IAP growth junction with IAP charts, and the cut-offs for BMI used
charts in which BMI can be read by plotting height and are more appropriate for Asian Indian children, who have
weight without the need to calculate BMI. The tool a higher body fat for a given BMI. However, it is important
demonstrated high sensitivity and specificity for screen- to remember that this is a quick screening tool and
ing children for underweight, overweight and obesity, children who are found to be abnormal on the tool or at
when tested against IAP BMI charts. borderline of categories should be rechecked on the IAP
BMI charts after calculating the BMI with standard
The limitations of the tool are that it is likely to
formula.
categorize children wrongly at extreme ends of height for
age, thus, too tall and very short children may be wrongly To conclude, we present a graphic BMI tool for
classified. The tool cannot be used in children younger screening for underweight, overweight and obesity to
than 8 years, and larger studies with a bigger sample size complement existing IAP charts. The tool is gender
are required for validation and generalization of the tool. specific and is based on height and weight, which
Weight in KG
Weight in KG
Height in CM Height in CM
Fig. 1 Body mass index screening tool for girls aged 8-18 years. Fig. 2 Body mass index screening tool for boys aged 8-18 years.

KHADILKAR, ET AL. BMI QUICK SCREENING TOOL

A body mass index (BMI) look-up tool using height and weight has been presented for screening for overweight,
obesity and underweight in children aged between 8 and18 years.
eliminates the need for calculation of BMI, and may help usage of growth charts. S Afr Fam Pract. 2015;57:219-22.
pediatricians to rapidly screen for perturbations in BMI in 7. Barlow SE, the Expert Committee. Expert committee
a busy clinical setting. recommendations regarding the prevention, assessment,
and treatment of child and adolescent overweight and
Ethics clearance: Institutional ethic committee of Jehangir obesity: Summary report. Pediatrics. 2007;120:S164-92.
Clinical Development Centre; dated June 21, 2016. 8. Expert Panel on Integrated Guidelines for Cardiovascular
Contributors: VK: concept and design of study, statistical Health and Risk Reduction in Children and Adolescents;
analysis and manuscript draft; NL, SC, AK: data collection, National Heart, Lung, and Blood Institute. Expert panel on
statistical analysis and manuscript draft. integrated guidelines for cardiovascular health and risk
Funding: None; Competing interest: None stated. reduction in children and adolescents: Summary report.
Pediatrics. 2011;128:S213-56.
REFERENCES
9. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M,
1. NCD Risk Factor Collaboration. Worldwide trends in Arslanian S, et al; IDF Consensus Group. The metabolic
body-mass index, underweight, overweight, and obesity syndrome in children and adolescents - an IDF consensus
from 1975 to 2016: A pooled analysis of 2416 population- report. Pediatr Diabetes. 2007;8:299-306.
based measurement studies in 128.9 million children, 10. Collins GS, Ogundimu EO, Altman DG. Sample size
adolescents, and adults. Lancet. 2017;390:2627-42. considerations for the external validation of a multivariable
2. Ranjani H, Mehreen TS, Pradeepa R, Anjana RM, Garg R, prognostic model: A resampling study. Stat Med. 2016;
Anand K, et al. Epidemiology of childhood overweight and 35:214-26.
obesity in India:vA systematic review. Indian J Med Res. 11. Lohiya N, Khadilkar V, Pawar S, Khadilkar A, Chiplonkar
2016;143:160-74. S, Jahagirdar R. Field testing IAP 2015 charts. Indian J
3. Liang Y, Hou D, Zhao X, Wang L, Hu Y, Liu J, et al. Child- Pediatr. 2018;85:723-8.
hood obesity affects adult metabolic syndrome and 12. de Onis M, Wijnhoven TMA, Onyango AW. Worldwide
diabetes. Endocrine. 2015;50:87-92. practices in child growth monitoring. J Pediatr. 2004;144:
4. Dasgupta A, Butt A, Saha TK, Basu G, Chattopadhyay A, 4610-5.
Mukherjee A. Assessment of malnutrition among adole- 13. Almeida AC, Mendes LC, Sada IR, Ramos EG, Fonseca
scents: Can BMI be replaced by MUAC. Indian J VM, Peixoto MV. Use of a monitoring tool for growth and
Community Med. 2010;35:276-9. development in Brazilian children: Systematic literature
5. Indian Academy of Pediatrics Growth Charts Committee. review. Rev Paul Pediatr. 2016;34:122-31.
Khadilkar V, Yadav S, Agrawal KK, Tamboli S, Banerjee 14. Elizabeth KE. A novel growth assessment chart for
M, Cherian A, et al. Revised IAP growth charts for height, adolescent. Indian Pediatr. 2001; 38:1061-4.
weight and body mass index for 5- to 18-year-old Indian 15. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing
children. Indian Pediatr. 2015;52:47-55. a standard definition for child overweight and obesity
6. Smith S, Reji E. Doctor’s attitudes to and knowledge and worldwide: International survey. BMJ. 2000;320:1240-3.

RESEARCH PAPER
Progression of Thyrotropinemia in Overweight and Obese Children From

Puducherry, India
SRINIVASAN THIAGARAJAN,1 THIRUNAVUKKARASU ARUN BABU2 AND RAJESHWAR BALAJI1
From Departments of Pediatrics, 1Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry, India; and
2All India Institute of Medical Sciences, Mangalagiri, Andhra Pradesh, India.
Correspondence to: Objective: To assess the progression of thyrotropinemia to overt hypothyroidism in

Dr Thirunavukarasu Arun Babu, overweight and obese children. Methods: 150 overweight and obese children aged 5-15
Associate Professor, Department of years were enrolled. Free T4 and thyroid stimulating hormone (TSH) were done at
enrollment and for those with TSH >5 mIU/L, TSH levels were repeated after 1 year.
Pediatrics, AIIMS, Mangalagiri, 522
Results: The mean (SD) body mass index (BMI) and TSH were 23.8 (3.19) kg/m2 and 2.70
503, Andhra Pradesh, India. (2.44) mIU/L, respectively. 17 children had thyrotropinemia (TSH between 10-15mIU/L); 10
*babuarun@yahoo.co.in (84.6%) of these children attained normal TSH levels at one year follow-up, and none
Received: June 06, 2019; progressed to overt hypothyroidism (TSH >15 mlU/L). Conclusion: Levels of 5-15 mIU/L
Initial review: October 09, 2019; are common in asymptomatic overweight and obese children. Majority of these children
Accepted: April 29, 2020. revert back to normal TSH levels on follow-up.
Keywords: Body mass index, Metabolic syndrome, Sub-clinical hypothyroidism, Thyroid
stimulating hormone.
C
omprehensive National Nutrition Survey obese children [2].Though there are various studies
(CNNS) 2016-18 reported that 4% of all school evaluating the intriguing relationship between fT4 and BMI
age children and 5% of adolescents were in childhood obesity, the findings are inconsistent [6-8].
overweight based on body mass index (BMI) Therefore, we studied the progression of thyrotropinemia
[1]. Subclinical hypothyroidism (SCH) is very common in (SCH) to overt hypothyroidism in obese and overweight
overweight and obese children and has an estimated children.
prevalence of about 9% compared to 6.1% in non-obese
children in India [2-4]. Risk factors for SCH are female sex, METHODS
Hashimoto thyroiditis, reduced iodide intake, radiation This longitudinal study was conducted from July, 2018 to
exposure, etc [2]. July, 2019 at a tertiary care pediatric hospital in Puducherry,
Diagnosing SCH in obese children remains contro- India. Children between 5-15 years of age attending the
versial as increased TSH levels (thyrotropinemia) are pediatric out patient department with body mass index
frequently present in obese children [4,5]. Although, the (BMI) more than 23 kg/m2 adult equivalent according to
exact mechanism of TSH elevation in obesity is unclear, standards for Indian children [10]. Children with BMI
some studies have attributed thyrotropinemia to increased between 23 to 27 kg/m2and >27 kg/m2 were categorized as
deiodinase levels converting T4 to T3 as a compensatory overweight and obese, respectively. Children on anti-
mechanism to increase basal metabolic rate, and reduced thyroid medication, family history of thyroid disorders, and
expression of TSH and T4 receptors in adipose tissue of sick children with acute illness requiring admission were
obese children [6]. Two large population-based studies excluded from the study. Approval from Institute’s research
from India reporting normograms for TSH in normal Indian and ethics committee were obtained before commencement
children are available [3], but there is no consensus in cut- of the study. Informed written consent was obtained from
off levels of TSH for obese children [7,8]. the parents and assent from older children.
Thyroxine replacement for marginal elevations of TSH All children were checked for presence of goiter and
in childhood obesity has questionable benefits [9]. Obesity symptoms of hypothyroidism like constipation, dry skin,
may be associated with TSH surge but it does not signify cold intolerance, hair loss, hoarse voice and growth
hypothyroidism in all cases. It is unclear if SCH retardation.Weight, height, waist circumference and hip
(thyrotropinemia) progresses into overt hypothyroidism in circumference measurements were recorded. Enrolled

THIAGARAJAN, ET AL. THYROTROPINEMIA IN OVERWEIGHT CHILDREN
children were screened for hypothyroidism with free T4 Table I Baseline and Follow-up Body Mass Index (BMI) in
(fT4) and TSH values following overnight fasting of 12 Overweight and Obese Children Aged 5-15 Year With
hour. fT4 and TSH levels were estimated by chemilumine- Initial Thyroid Stimulating Hormone Level 5-15 mU/L
scence method using immunoassay analyzer. Based on a (N=17)
school based Indian study, the reference values of mean BMI, kg/m2 P value
fT4 were 1.13-1.34 ng/dL for boys and 1.11-1.22 ng/dL for Baseline TSH, Baseline Follow up
girls, and TSH 2.57-3.6 mIU/l for boys and 1.83-3.58 mIU/L mIU/L mean (SD) mean (SD)
for girls [4]. Children with TSH >15 mIU/L irrespective of
TSH 5-10 22.48 (2.2) 22.49 (2.1) 0.56
symptoms and TSH between 10 -15 mIU/L with symptoms
of hypothyroidism were treated with thyroxine [11]. TSH 10-15 25.62 (3.4) 25.59 (3.1) 0.42
Lifestyle modifications like healthy eating patterns,
increased physical activity and decreased sedentary the follow-up period of 3 months to 1 year, which was
behavior were advised to all participants. Children with similar to our findings [14]. TSH levels decreased in more
SCH (TSH 5-15 mIU/L) were followed up for a period of than 80% of obese children following life style
one year and serum TSH levels were repeated. interventions for obesity without thyroxine therapy [15].
Weight reduction and TSH normalization were attained
Statistical analysis: Data entry was done in MS Excel only with diet and life style modifications [15]. In our
2010. Data was analyzed using SPSS version 16.0. study, though TSH levels normalized in most of the
Pearson correlation coefficient was used for correlation children, majority had no weight reduction on follow-up.
studies.Wilcoxon signed rank test was applied for This was mainly attributed to lack of compliance to life
comparing baseline and follow-up variables. Values of style modifications and lack of regular follow-up.
P<0.05 were considered statistically significant.
In this study, we found poor correlation between BMI
RESULTS and TSH/T4 levels, whereas Ghergherehchi, et al. [12]
Among 150 overweight and obese children (49.3% males; demonstrated that levels of TSH and fT4 were signi-
mean age, 10.2 year) included in our study, 132 (88%) ficantly higher in children with obesity compared with the
children were found to have a TSH value of 0-5 mIU/L control [12]. In a study published from South Korea, BMI
(euthyroid); 17 (11.3%) had a TSH value corresponding was positively correlated with serum concentrations of
to SCH levels with 15 (10%) having TSH between 5-10 TSH and negatively correlated with serum concentrations
mIU/L). One child (0.66%) had TSH >15 mIU/L diagnosed of fT4 after adjusting for age [13]. In this study, we could
as overt hypothyroidism and started on thyroxine. The not demonstrate the relationship between baseline BMI
mean fT4 in subgroups with TSH 5-10 and 10-15 mIU/L and baseline TSH, which is discordant with many similar
were 1.40 and 1.78 ng/dL, respectively. The mean (SD) studies, which have confirmed the increasing TSH levels
BMI and TSH of the study group were 23.78 (3.19) and with BMI. Similarly, fT4 levels were not associated with
2.70 (2.44) mIU/L, respectively. There was no association BMI in our study though some studies revealed a
of TSH level with overweight or obese children (P=0.56). positive or negative correlation with BMI [12,13].
The correlation coefficient of BMI with fT4 and TSH were Relatively smaller sample size and lack of autoimmune
r=0.08 and r=0.016 (both P >0.05), respectively. thyroid profile data in the study population are some of
On follow-up of 17 children with SCH,10 (84.6%) had the limitations of this study. Further multi-centric studies
become euthyroid and 7 (15.4%) remained at subclinical with long term follow-up are needed to detail the cause of
hypothyroid levels. None progressed to overt hypothy- hypothyroidism among obese children, and course of
roidism.The mean (SD) baseline and following TSH thyrotropinemia in adolescence and young adulthood.
values were 6.33 (2.15) and 4.92 (2.14) (P=0.47). Acknowledgement: Mrs Poovitha, Statistician, Indira Gandhi
Comparison of mean baseline BMI with follow-up BMI is Medical College and Research Institute, Puducherry, India.
given in Table I. No correlation was found between Contributors: ST,AT: conceived the study; ST, RB: collected data
weight loss and TSH change (r=0.138; P=0.598). and managed the cases; ST,RB: reviewed the literature and
drafted the initial version of the manuscript; AT contributed to
DISCUSSION literature review and critically revised the manuscript. All authors
contributed to drafting of the manuscript and approved the final
Our study revealed majority (84.6 %) of obese kids with version of the manuscript.
SCH (TSH 5-15 mIU/L) reverted back to euthyroid state Ethics approval: Institute Ethics committee IGMC&RI,
within one year. In another study from India, among 40 Puducherry; No. 06/IEC/IGMC&RI/F-7/2018 dated June 6,
children (aged 2-16 years) presenting with subclinical 2018.
hypothyroidism, majority (52.5%) became euthyroid after Funding: None; Competing interests: None stated.

THIAGARAJAN, ET AL. THYROTROPINEMIA IN OVERWEIGHT CHILDREN

• Subclinical hypothyroid levels of TSH (5-15 mIU/L) were common in overweight and obese children, and
reverted back to normal after a one-year follow-up.
REFERENCES 9. Wasniewska M, Corrias A, Aversa T, Valenzise M, Mussa

A, De Martino L, et al. Comparative evaluation of therapy
1. Ministry of Health and Family Welfare (MoHFW), with L-Thyroxine versus no treatment in children with
Government of India, UNICEF andpopulation Council, idiopathic and mild subclinical hypothyroidism. Horm Res
2019. Comprehensive National Nutrition Survey (CNNS) Paediatr. 2012;77:376-81.
National Report, New Delhi. Available from: https:// 10. Khadilkar V, Yadav S, Agrawal KK, Tamboli S, Banerjee
www.popcouncil.org/uploads/pdfs/2019RH_CNNS M, Cherian A, et al. Revised IAP growth charts for height,
report.pdf. Accessed January 6, 2020. weight and body mass index for 5- to 18-year-old Indian
2. Shriraam M, Sridhar M. Subclinical hypothyroidism in children. Indian Pediatr. 2015;52:47-55.
children. Indian Pediatr. 2014;51:889-95. 11. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola
3. Marwaha RK, Tandon N, Desai A, et al. Reference range of AR, Celi FS, et al. Guidelines for the Treatment of Hypo-
thyroid hormones in normal Indian school-age children. thyroidism: Prepared by the American Thyroid Asso-
ClinEndocrinol.2008; 68:369-74. ciation Task Force on Thyroid Hormone Replacement.
4. Marwaha RK, Tandon N, Garg MK, Ganie MA, Narang A, Thyroid. 2014;24:1670-751.
Mehan N, et al. Impact of body mass index on thyroid fun- 12. Ghergherehchi R, Nazanin H. Thyroid hormonal status
ctions in Indian children. ClinEndocrinol. 2013;79:424-8. among children with obesity. Ther Adv Endocrinol Metab.
5. Thiagarajan S, Arunbabu T, Balaji R. Subclinical hypo- 2015;6:51-5.
thyroidism in obese South Indian children. Indian J Pediatr. 13. Jin HY. Prevalence of subclinical hypothyroidism in obese
2019;86:662. children or adolescents and association between thyroid
6. Longhi S, Radetti G. Thyroid function and obesity. J Clin hormone and the components of metabolic syndrome. J
Res Pediatr Endocrinol. 2013;5:40-4. Paediatr Child Health. 2018;54:975-80.
7. Aypak C, Turedi O, Yuce A, Gorepelioglu S. Thyroid- 14. Sridhar M, Mahadevan S, Vishwanathan L, Subbarayan A.
stimulating hormone (TSH) level in nutritionally obese Subclinical hypothyroidism: A prospective observational
children and metabolic co-morbidity. J Pediatr Endocrinol study from Southern India. Indian Pediatr.2014;55:219-21.
Metab. 2013;26:703-8. 15. Matusik P, Gawlik A, Januszek-Trzciakowska A,
8. Reinehr T, de Sousa G, Andler. Hyperthyrotropinemia Malecka-Tendera E. Isolated subclinical hyperthyrotro-
in obese children is reversible after weight loss and is not pinemiain obese children: Does levothyroxine (LT4)
related to lipids. J Clin Endocrinol Metab. 2006;91: improve weight reduction during combined behavioral
3088-91. therapy? Int J Endocrinol. 2015;2015:792509.

RESEARCH PAPER
Weight of Schoolbags Among Indian Schoolchildren in Pune and Hyderabad

RAJNEESH K JOSHI,1 SAURABH MAHAJAN,1 A YASHOWANTH RAO,2 LIKITH POLISETTY1 AND MADHURI KANITKAR3
From Departments of 1Community Medicine, and 3Pediatric Nephrology, Armed Forces Medical College, Pune; and 2Department of
Pediatrics, Kameneni Academy of Medical Sciences and Research Centre, Hyderabad, Andhra Pradesh, India.
Correspondence to: Dr Rajneesh K Objective: This study was done to determine proportion of children carrying heavy school
Joshi, Department of Community bags and to compare new guidelines issued by Government of India on school bag weight
Medicine, Armed Forces Medical limit, based on class of the child with previous guidelines based on child’s weight. Methods:
A cross-sectional study was done among students of schools from two cities of India –
College, Pune, India.
Pune and Hyderabad. Weight of school bag of 1321 children was measured and classified
Received: April 15, 2019; as ‘heavy’ or ‘normal’ based on existing as well as new guidelines. Agreement between two
Initial review: September 19, 2019; guidelines was also calculated. Results: In our study, 722 (77.2%) out of 935 students
Accepted: July 06, 2020. from class 1-10 were found to be carrying ‘heavy’ school bags. Kappa coefficient for
agreement between two guidelines was 0.55 (0.47,0.60) indicating moderately strong
agreement. Conclusions: Large proportion of school children are carrying school bags
with weight beyond permissible limits. There is a need for all stake holders to take steps to
reduce weight of school bags.
Keywords: Bags, Child, Education, India, School.
I
n present times, school children have to carry heavy in Pune and Hyderabad city of India. School children
schoolbags due to number of books, notebooks and studying in all grades of selected schools i.e. from
variety of other materials they are required to bring Nursery to 10th standard were included in this study .
in their school. Heavy school bags can lead to Minimum sample size required to estimate proportion of
number of musculoskeletal problems like backache, school children carrying heavy school bags in our study,
shoulder pain, pain in hand and wrist, and spinal assuming that proportion to be 76% [10], with 95%
deformities among children [1-6]. Heavy school bags confidence level and 2.5% error of margin was 1121.
have also been found to be associated with poor Assuming non-response rate of 15%, we planned to
educational outcomes and absenteeism. There are laid include 1325 students in this study. Simple random samp-
down guidelines that school bag should not be more than ling was used to select the students for this study.
10% of child’s weight [2,7,8] and there shall not be any
Administrative permissions were taken from res-
school bag for a child studying in nursery and
pective school authorities to carry out this study .
kindergarten classes [9]. However, various studies carried
Institutional Ethics Committee approval was also
out in India as well as in other countries have brought out
obtained. Parents’ consent and children assent was taken
that school children are carrying school bags with weight
for participation in this study . Students particulars
beyond permissible limits [1-6,10-12]. Recently, Ministry
including date of birth were obtained from school records.
of Human Resource Development, Government of India
A digital weighing machine was used to measure weight
issued new guide-lines for school bag weight [13].
of students with bag and without bag. Difference in these
According to these guidelines, maximum permissible
two weights was used to calculate weight of school bag.
weight of school bags has been specified according to
Shoes of students were removed before measuring
the class in which a child is studying. We carried out this
weight. We used two criteria to classify school bag as
study on school bag weights of school children in India
‘heavy’: (i) Criterion 1 – According to child’s weight - If
to estimate proportion of children carrying schoolbags
school bag weight was more than 10% of child’s weight
heavier than recommen-ded weight as per previous as
[9]; and (ii) Criterion 2-According to class - If school bag
well as newer guidelines. We also investigated level of
weight was more than 1.5 kg for class 1 & 2, more than 3 kg
agreement between these two guidelines in our study.
for class 3-5, more than 4 kg for class 6-7, more than 4.5 kg
METHODS for class 8-9, and more than 5 kg for class 10th
[13].
This cross-sectional study was done in selected schools Statistical analysis: Student t test was used to compare

JOSHI, ET AL. WEIGHT OF SCHOOLBAGS
continuous variables between two groups. Kappa co- Table I Weight of Schoolbag in the Enrolled Children
efficient was used to measure agreement between two (N=1321)
guidelines regarding overweight of school bags. R Grade Number of Schoolbag Schoolbag weight
software ver 3.2.0 was used for data analysis. children weight (kg) as body weight
percentage (%)
RESULTS
Nursery 101 1.08 (0.40) 7.6 (2.9)
A total of 1321 students (708 male) participated in this
study, mean (SD) schoolbag weight was 3.81 (2.45) Kg. LKG 145 1.94 (0.58) 11.9 (3.92)
Distribution of students as per different classes is shown in UKG 140 2.18 (0.54) 12.3 (3.78)
Table I. Class 8 students had highest mean school bag 1 82 3.15 (0.91) 14.9 (5.37)
weight [8.05 (2.87) kg]. However, class 6 students were 2 145 3.33 (1.12) 14.9 (5.55)
found to be carrying highest school bag weight in terms of
3 147 3.40 (1.21) 14.4 (6.11)
their body weight [21.65 (8.93)%]. Mean school bag weight
as per different classes is shown inTable I and Figs. 1 and 4 132 3.65 (1.26) 13.8 (5.76)
2. There was no significant difference in mean (SD) school 5 186 4.15 (1.44) 13.8 (6.12)
bag weight of boys and girls in our study [3.92 (2.67) kg vs 6 38 6.89 (2.53) 21.6 (8.93)
3.68 (2.17) kg, P=0.07], or mean (SD) school bag weight as
7 41 7.78 (2.86) 20.4 (9.14)
percentage of body weight [13.9 (6.55)vs 13.9 (5.95); P=0.9].
8 53 8.05 (2.87) 18.9 (7.86)
According to guidelines, children studying in nursery
9 50 7.46 (2.38) 16.9 (6.02)
and kindergarten should not be carrying any schoolbag.
However, in our study we found that children studying in 10 61 7.56 (2.15) 12.0 (4.0)
these pre-primary classes were also carrying school bags LKG: Lower kindergarten; UKG: Upper kindergarten; values in
with weights as mentioned inTable I. Hence, we assumed mean (SD).
that 100% of these pre-primary school children were
carrying ‘heavy’ school bags. We excluded these children
Although Criterion 1 and Criterion 2 classified almost
from further analysis.
equal number of school bags (724 and 722, respectively)
We used two criteria to classify school bag weight as as ‘heavy’; only 647 bags were classified as heavy by
‘high’ for school children studying in grades 1-10. We both criteria (Table III). Overall, agreement in these two
found that more than 77% school children were carrying criteria for classification of schoolbag weight as heavy or
school bag with more than recommended weight. otherwise was 83.7% [Kappa co-efficient (95% CI): 0.55
Distribution of these students as per their grade is shown (0.47, 0.60)] indicating moderately strong agreement in
in Table II. these two guidelines.
Fig. 1 Boxplot showing weight of school bag (in kgs) for different Fig. 2 Boxplot showing weight of school bag (as percentage of
grades. body weight) in students of different grades.

Table II Distribution of Children Carrying Heavy School major limitation of this study is that we have included
Bags in Pune and Hyderabad (N=935) selected schools from two cities only; hence, generali-
Grade No. Number (%) carrying zability of study findings is limited.
heavy school bags*
Our findings are similar to study by Oka,et al. [10] in
M F Total Criterion I Criterion II two urban areas which also found 76% of schoolchildren
n=724 n=722
carrying heavy bags, though another study [12] in rural
1 35 47 82 67 (81.7) 79 (96.3) Maharashtra found less than 50% of students with heavy
2 80 65 145 111 (76.6) 138 (95.2) school bags. These variations indicate that there may be
3 79 68 147 108 (73.5) 78 (53.1) difference in number of books and notebooks being
carried by students in urban and rural area schools. Few
4 77 55 132 102 (77.3) 82 (62.1)
studies [5,6] had reported that boys carry heavier school
5 103 83 186 129 (69.4) 131 (70.4)
bags as compared to girls; however, we did not find any
6 22 16 38 35 (92.1) 31 (81.6) significant difference in weight of school bags of boys and
7 21 20 41 38 (92.7) 36 (87.8) girls. Our finding of significant increase in school bag
8 26 27 53 49 (92.5) 50 (94.3) weight in higher classes of school is similar to previous
9 28 22 50 46 (92.0) 47 (94.0) studies [3,11].
10 29 32 61 39 (63.9) 50 (82.0) Our findings highlight the need to implement Govern-
*Criterion I -Bag weight >10% of Bodyweight [9] and Criterion II – Bag ment guidelines regarding school bag weight in true spirit.
weight more than guidelines issued by Government of India [13]. Education department can make curriculum more practical
problems oriented and less theory intensive, which will help
in reducing the burden of books children have to carry .
DISCUSSION Schools can also make timetable for classes in such a way
In this study, we observed that weight of school bags was that students need to bring books related to few subjects
much higher than recommended weight-limit. Though only on a given day. Also, books and note books which
pre-primary students should not carry schoolbags, in our students may not require at home, can be kept in school
study all pre-primary students were carrying school bags itself. Use of papers and files instead of notebooks can also
with books and note-books. We found that very high help in reducing weight of school bags. Judicious use of
proportion of students in grades 1-10 were carrying computers and tablets in schools can also reduce the
heavy school bags, which should be a cause for concern. burden of books for students. Parents also need to ensure
We also observed that problem of heavy weight of school that their child carried minimum required books and
bags increased from class 6 onwards. Similar proportion notebooks to school, as many times children tend to take
of children were classified as carrying heavy school bags all books and notebooks to school.
by both the guidelines for school bag weights and there Contributors: RKJ: study design, data collection and analysis,
was moderately strong agreement between these two preparation of manuscript; SM: Data collection, analysis and
guidelines. manuscript preparation; AYR: study conceptualization, data
collection and critical revision of manuscript; LP: study design,
This is the first study to evaluate new guidelines data collection and manuscript preparation; MK: Study concep-
issued by Government of India regarding schoolbag tualization and design, data collection, interpretation and critical
weight with previous guidelines and we included revision of manuscript. All authors approved the final version of
students from all classes of school in our study.However, manuscript and agree to be accountable for authenticity and
integrity of the work.
Table III Agreement Between the Two Criteria for
Classifying Schoolbag Weight as ‘Heavy’ or ‘Normal’ REFERENCES
Criterion 1 1. Aundhakar C, Bahatkar K, Padiyar M, Jeswani D, Colaco
Heavy Normal S. Back pain in children associated with backpacks. Indian J
(n=724) (n=211) Pain. 2015;29:29-31.
2. Janakiraman B, Ravichandran H, Demeke S, Fasika S.
Criterion 2 Heavy (n=722) 647 75
Reported influences of backpack loads on postural
Normal (n=213) 77 136 deviation among school children: A systematic review. J
Criterion I -Bag weight >10% of Bodyweight [9] and Criterion 2 – Educ Health Promot. 2017;6:41.
Bag weight more than guidelines issued by Government of India 3. Balamurugan J. School bags and musculoskeletal pain
[13]. among elementary school children in Chennai city. Int J


• New guidelines regarding schoolbag weight based on class of child have moderately strong agreement with
previous guidelines based on child’s weight.
Med Sci Clin Invent. 2014;1:302-9. 9. Government of India.The Children School Bags (Limitation
4. Ramprasad M, Alias J, Raghuveer AK. Effect of backpack on weight) Bill 2006. Availablefrom:http://164.100.24.219/
weight on postural angles in preadolescent children. Indian billstexts/rsbilltexts/AsIntroduced/LXXXVI_ % 202006.pdf.
Pediatr. 2010;47:575-80. Accessed Sepember 17, 2019.
5. Brzek A, Dworrak T, Strauss M, Sanchis GF, Sabbah I, 10. Oka GA, Ranade AS, Kulkarni AA. Back pain and school
Dworrak B, et al. The weight of pupils’ schoolbags in early bag weight - a study on Indian children and review of
school age and its influence on body posture. BMC literature. J Pediatr Orthop B. 2019;28:397-404.
Musculoskelet Disord. 2017;18:117. 11. Mohan M, Singh U, Quddus N. Effect of backpack loading
6. Mandic S, Keller R, Bengoechea EG, Moore A, Coppell KJ. on cervical and shoulder posture in Indian school children.
School bag weight as a barrier to active transport to school Indian J Physiother Occup Therapy. 2007;1:3-12.
among New Zealand adolescents. Children. 2018;5:129. 12. Ashtekar SV, Powar JD, Aqsa S, Padhyegurjar SB,
7. Bauer DH, Freivalds A. Backpack load limit recommen-dation Padhyegurjar MS, Banginwar A. Schoolbag-weights and
for middle school students based on physiological and musculo-skeletal complaints in three schools in rural
psychophysical measurements. Work. 2009;32:339-50. Maharashtra. Natl J Community Med. 2017;8:572-8.
8. Department of Education Maharashtra State Government. 13. Directorate of Education, Government of National Capital
Government resolution regarding reducing bag-weights Territory of Delhi. Reducing the weight of school bags in
among school 2016. Available from:https://www.maharas primary and secondary schools. Availablefrom:http://www.
htra.gov.in/Site/Upload/Government%20Resolutions/ Mar edudel.nic.in/upload/upload_2017-18/1667dt_30112018.
athi/201507171135220721.pdf. Accessed July 15, 2019. PDF. Accessed January 25, 2020.
ADVERTISEMENT
Golden Opportunity for Budding Researchers
Indian Pediatrics Case Reports (IPCaRes)

First Issue in February, 2021
• For Pediatric Medicine, Pediatric Surgery, Pediatric subspecialties & Neonatology
• Primarily dedicated to Case-reports, Case-series, Images, and clinical videos
• Intimidated at the thought of writing? Start small.
Share personal perspectives (Close encounters) and brief humorous anecdotes (Grin and share it)
• Solve ‘Dr Watson’s Clinical Mystery’, ‘Neonatal Quiz’ and ‘Clinical Crossword’ and find your name
displayed on the website.
• Improve your clinical approach with ‘Forensic Files’ and ‘Radiological rounds’
• Learn about the past in ‘The IP Chronicles’and the present in ‘News excerpts.’
• Wondering which book to read? Let our book review help you decide!
• Peer reviewed, quarterly online and print journal
• E-copy free-of-cost to all IAP members
• Free full-text html at Website
• Priced complete issues/single articles on demand
• Authors are invited to send an e-mail to ipcares2020@gmail.com citing section of interest and
we will provide you with the relevant instructions for authors and forms.
Submit Your Manuscripts at the Earliest

RESEARCH PAPER
Epidemiological and Clinical Characteristics of COVID-19 in Indian

Children in the Initial Phase of the Pandemic
BHAKTI SARANGI, VENKAT SANDEEP REDDY, JITENDRA S OSWAL, NANDINI MALSHE, AJINKYA PATIL, MANOJIT
CHAKRABORTY AND SANJAY LALWANI
From Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India.
Correspondence to: Jitendra S Oswal, Objective: To assess the epidemiological and clinical characteristics of pediatric inpatients
Professor, Department of Pediatrics, with COVID-19, early in the pandemic. Methods: Clinical and laboratory profile and
Bharati Vidyapeeth Medical College outcomes were studied for children (aged 1 month - 18 years) presenting between 1 April,
2020 and 20 May, 2020 with positive nasopharyngeal swab for SARS-CoV-2 by RT-PCR.
and Hospital, Pune 411043,
Results: 50 children (56% male) with median (IQR) age of 6 (2-12) years were included.
Maharashtra, India. Majority (56%) were from families belonging to Kuppuswamy upper lower socioeconomic
jsoswal@gmail.com class. 45 (90%) had positive household contact, and 33 (66%) had overcrowding at home.
Received: June 08, 2020; 29 (58%) children were asymptomatic while 20 (40%) had mild symptoms. Fever, cough,
Initial review: June 19, 2020; and sore throat were the most common symptoms. High C-reactive protein levels were seen
Accepted: July 28, 2020. in 15 (30%) children. There was no mortality. Conclusion: The disease burden appears
high in lower socio-economic group with majority having a positive household contact. Milder
disease pattern in the pediatric age group is reiterated.
Keywords: Management, RT-PCR, SARS-CoV-2, Symptoms, Outcome.
Published online: July 28, 2020; PII: S097475591600218
C
oronavirus disease 2019 (COVID-19), caused years of age. Detailed information including demographic
by severe acute respiratory syndrome data, travel and contact history, living conditions and
coronavirus 2 (SARS-CoV-2), has been in overcrowding, symptoms, and presence of co-morbid
circulation for more than six months now [1]. conditions were taken. The children were examined and
Though there have been a growing number of studies categorized as per degree of severity based on standard
focused on COVID-19, limited data is available on criteria [2].
epidemiological features, clinical manifestations, and
transmission patterns in children with COVID-19, more so Baseline laboratory parameters (complete hemogram
from India. Early observations in a pandemic are pivotal in and C-reactive protein) were evaluated and repeated as
improving the understanding of the physiological required. Chest radiograph was done in all symptomatic
patterns and varied clinical profiles, so as to improve early children. On chest X-ray each lung was divided into three
recognition and appropriate management. We, therefore, zones. Each zone was given a score of 1 if there was any
describe the clinical and epidemiological features of opacity and 0 if there were none. Total score of 3 was
pediatric patients seen at a single tertiary-care institution. considered as 50% involvement [3]. All children admitted
were managed as per the hospital protocol. The children
METHODS were monitored daily for changes in disease severity.
Discharge from hospital was as per prescribed World
This was a cross-sectional study conducted in a Health Organization (WHO) guidelines which stated that
dedicated pediatric COVID-19 center in Pune, asymptomatic children who tested negative for two
Maharashtra between 1 April, 2020 and 20 May, 2020. nasopharyngeal swabs taken 24 hours apart after day 14
Prior approval was taken from the institutional ethics of illness were fit for discharge [4]. Overcrowding was
committee. All children between one month and 18 years defined based on persons per room criteria [5].
of age who tested positive by the RT- PCR technique for
nasopharyngeal swab were included in the study – these Statistical analyses: The data were analyzed using the
also included asymptomatic children as per the Statistical Package for Social Sciences (SPSS) software
management guidelines in force. Written informed version 25.0. Spearman’s Rho correlation coefficient was
consent was taken from the parents of all children and used to determine the correlation with disease severity. A
assent was taken from children who were greater than 9 P value <0.05 was considered significant.

SARANGI, ET AL. COVID-19 IN INDIAN CHILDREN
RESULTS less than five years of age accounted for nearly half the
cases. This can be attributed to the inability of this age
A total of 178 children presented to us with suggestive
group to comprehend and follow social distancing norms
features during the study duration, of which, 153 were
and their frequent close contact with parents.
negative and 25 were positive for SARS-CoV-2 by RT-
PCR. Another 25 children with a positive RT-PCR were Pediatric observational studies published early in the
referred from other hospitals. Thus, a total of 50 children spread across China reported similar clinical findings with
(56% males) with median (IQR) age of 6 (2-12) years were fever being the most common symptom followed by
included. Majority (82%) of the cases hailed from cough and sore throat [7]. A recent meta-analysis has also
containment zones in Pune. There was history of positive shown that most of the patients have mild to moderate
household contact in 45 (90%) children; with 42 having disease (96%) with only 1% of all the symptomatic
family members with mild illness and three with severe pediatric cases being critically sick [8]. The reported
illness. Travel history to affected area was documented in mortality rate of COVID-19 in children is less than 1% [9].
only one child (Table I). Various hypotheses have been proposed for the lesser
disease severity in children [10], though a definite answer
More than half (58%) of the children were
is still awaited.
asymptomatic while 20 (40%) had mild symptoms. In
symptomatic children, fever was the chief complaint in 17
Table I Epidemiological and Clinical Characteristics of
(34%). None of the children had hypoxemia measured by Children With SARS-CoV-2 Infection in Pune, 2020 (N=50)
pulse oximetry. Only two children had co-morbidities; one
child had history of simple febrile seizures, and another Parameters No. (%)
had underlying type I diabetes mellitus and had Male 28 (56)
presented with diabetic ketoacidosis. Immunization was Age
complete in 32 (64%) of the children as per universal
1 mo to 1 y 9 (18)
immunization program, and 49 (98%) children had a BCG
scar. >1 to 5 y 15 (30)
>5 to 10 y 12 (24)
The mean (SD) leucocyte count was 8864 (3727.2)
>10 to 15 y 11 (22)
X109/L (range, 3300-19300 X109/L). Leucopenia was seen
in 3 (6%) children while leukocytosis was seen in 13 (26%) >15 to 18 y 3 (6)
children. Lymphopenia, eosinopenia and thrombo- Weight-for-age (3-97centile) 45 (90)
cytopenia were not seen in any child. Neutrophil- Overcrowding 33 (66)
lymphocyte-ratio (NLR) (r=0.35, P=0.01) and lymphocyte- Contact with patient of COVID- 19 45 (90)
monocyte-ratio (LMR) (r=-0.31, P=0.03) showed a
Socio-economic status*
significant correlation with the severity of the illness,
while platelet-lymphocyte ratio (PLR) (r=0.28, P=0.06) and Upper lower 28 (56)
CRP (r=0.05, P=0.73) did not show any correlation with Lower middle 17 (54)
severity of the disease. Upper middle 5 (10)
Severity of illness
Chest radiograph was done in 20 (95.2%) of 21
symptomatic children. It was found to be normal in 18 Asymptomatic 29 (58)
(85.7%), while two showed bilateral lower zone haziness Mild 20 (40)
(<50%). The disease category for all patients remained Moderate 1 (2)
same all through the hospital stay and no mortality was Severe 0 (0)
seen.
Symptoms
DISCUSSION Fever 17 (34)
Majority of children in our study were detected in the Cough 8 (16)
identified containment zones, most of them reporting Sore throat 7 (14)
exposure to a positive household contact. Majority of the Myalgia 4 (8)
children were either asymptomatic or had mild disease. Diarrhea 2 (4)
Most children were from lower socio-economic Headache 2 (4)
groups, a pattern also witnessed in other countries [6]. *As per Kuppuswamy classification; One child each had rash and
Though the disease was seen in all age groups, children conjunctivitis.


• Majority of Indian children with SARS-CoV-2 infection had a mild course of disease during the initial stages
of the pandemic.
Malnutrition has been deemed a risk factor in adult Table II Laboratory Investigations of Children With SARS-
COVID-19 [11]. In children, malnutrition is known to foster CoV-2 Infection in Pune, 2020 (N=50)
infections; however, in this study, majority of the children Parameter Value
were well-nourished as per weight-for-age criteria. The
hematological profile of adults with COVID-19 has Absolute neutrophil count (x 109/L) 2480 (1995.5-3339)
demonstrated leucopenia with associated neutrophilia, Absolute lymphocyte count (x 109/L) 4071 (2912-5964)
lymphopenia; eosinopenia and thrombocytopenia. Also, Absolute monocyte count (x 109/L) 576 (402.5-744)
higher NLR, LMR and PLR have been associated with Absolute eosinophil count (x 109/L) 156 (68.5-437.5)
severe disease and used for prognostication [12]. Leucopenia* 3 (6)
Leucopenia, however, was seen in only 6% of our children High C-reactive protein* 15 (30)
and there was no evidence of lymphopenia, thrombo-
cytopenia or eosinopenia. Increasing NLR in our study All values in median (IQR) except *no.(%); leucopenia-leucocyte
count <4000×109/L; High C-reactive protein- value >6 mg/dL.
showed a moderate positive correlation coefficient while
LMR showed a negative correlation. High CRP values have
now become synonymous with severe COVID-19 infection In conclusion, our study shows that there is a higher
among adults as seen in majority of the studies [13]. The disease burden in lower-socioeconomic groups with
value of CRP did not correlate with disease severity in our majority of children having a positive household contact.
study. These discordant results may be due to the majority A milder disease pattern is seen in majority of children
of our patients being asymptomatic or mildly symptomatic, with COVID-19.
or due to a different history of antigen exposure and
immune response. Ethical approval: Institutional Ethics Committee of Bharati
Vidyapeeth Medical College and Hospital; No. BVUDMC/IEC/
Repeat RT-PCR of nasopharyngeal swab was done on 1B, dated 10 April, 2020.
day 14 and 15 to check for infectivity status. All the Contributors: VSR,BS,AP,MC: management of the patients;
children except one tested negative by RT-PCR on both VSR,BS: collected the data, reviewed the literature and drafted
the days. For the child who tested positive for one swab, a the first version of the manuscript; BS,JSO,NM,SL:
conceptualized the study, reviewed the literature, revised the
repeat swab was negative after three days, thus
manuscript and critically reviewed the manuscript. All authors
indicating that clearance of viral load may vary in different
contributed to manuscript preparation and approved the final
individuals. The degree of infectivity of these individuals version of the manuscript.
after 14 days remains questionable as RT-PCR detects Funding: None; Competing interests: None stated.
genetic fragments of the virus and cannot distinguish
REFERENCES
between dead or live virus [14]. In such scenarios, doing a
viral culture may be the plausible method of detecting live 1. Riou J, Althaus CL. Pattern of early human-to-human
virus and demonstrating continued infectivity. As transmission of Wuhan 2019 novel coronavirus (2019-
performing a viral culture is difficult and requires nCoV), December 2019 to January 2020. Euro Surveill.
advanced laboratory facilities, using GeneXpert platform 2020;25:2000058
2. Guidelines On Clinical Management Of COVID-19.
with (cycle threshold) Ct values ≥ 24 may also be
Government of India Ministry of Health & Family Welfare
beneficial for predicting lack of infectivity [15].
Directorate General of Health Services (EMR Division),
The findings of our study are limited by the size of the pp.3-5. Available at: https://www.mohfw.gov.in/pdf/
cohort and may require further validation by a study with GuidelinesonClinicalManagementofCOVID 1912020.pdf.
Accessed July 27, 2020.
a larger sample size. Being a study in the initial phase of
3. Toussie D, Voutsinas N, Finkelstein M, Cedillo M, Manna
the pandemic with lockdown in place, it may not cover the
S, Maron S, et al. Clinical and chest radiography features
entire spectrum of clinical presentations, severity and determine patient outcomes in young and middle age adults
magnitude of SARS-CoV-2 in children from different with COVID-19. Radiol. 2020;201754.
geographical areas. We could also not collect data for 4. Global Surveillance for human infection with novel
calculation of body mass index (BMI) and Z-scores. coronavirus(2019-nCoV). Available from: https://

www.who.int/publications-detail/global-surveillance-for- 10. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N,

human-infection-with-novel-coronavirus-(2019-ncov). Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends
Accessed June 20, 2020 on ACE2 and TMPRSS2 and is blocked by a clinically
5. Park K. Environment and Health. In: Park K, ed. Park’s proven protease inhibitor. Cell. 2020;181:271-80.e8
Textbook of Preventive and Social Medicine. 23rd ed. 11. Li T, Zhang Y, Gong C, Wang J, Liu B, Shi L, et al.
Jabalpur: Bhanot Publishers; 2015.p.758. Prevalence of malnutrition and analysis of related factors in
6. Coronavirus Disease 2019 (COVID-19). Centers for elderly patients with COVID-19 in Wuhan, China. Eur J
Disease Control and Prevention. 2020. Available from: Clin Nutr. 2020;74:871-9.
https://www.cdc.gov/coronavirus/2019-ncov/need-extra- 12. Lagunas-Rangel FA. Neutrophil-to-lymphocyte ratio and
precautions/ racial-ethnic-minorities.html. Accessed June lymphocyte-to-C-reactive protein ratio in patients with
20, 2020. severe coronavirus disease 2019 (COVID-19): A meta-
7. Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and analysis. J Med Virol. 2020;10.1002/jmv.25819 [published
epidemiological features of 36 children with coronavirus online ahead of print, 2020 Apr 3].
disease 2019 (COVID-19) in Zhejiang, China: An obser- 13. Wang L. C-reactive protein levels in the early stage of
vational cohort study. Lancet Infect Dis. 2020;20:689-96. COVID-19. Med Mal Infect. 2020;50:332-4.
8. Meena J, Yadav J, Saini L, Yadav A, Kumar J. Clinical 14. Lauri A, Mariani PO. Potentials and limitations of
features and outcome of SARS-CoV-2 infection in children: molecular diagnostic methods in food safety. Genes Nutr.
A systematic review and meta-analysis. Indian Pediatr. 2008;4:1-12.
2020 Jun 24. S097475591600203 [Epub ahead of print]. 15. Bullard J, Dust K, Funk D, Strong JE, Alexander D, Garnett
9. COVID-19: Data Summary - NYC Health. Available from: L, et al. Predicting infectious SARS-CoV-2 from diagnostic
https://www1.nyc.gov/site/ doh/covid/ covid-19-data.page. samples. Clin Infect Dis. 2020;ciaa638 [published online
Accessed June 20, 2020 ahead of print, 2020 May 22].

RESEARCH PAPER
Maternal Occupational Tobacco Exposure and Newborn Umbilical Cord

Serum Leptin Concentration
SWATHI S RAO,1 A PREETHIKA,2 DENYA MARY YELDHO,1 Y SUNIL KUMAR1 AND RATHIKA D SHENOY1
From Department of 1Pediatrics and 2Central Research Laboratory, KS Hegde Medical Academy, Nitte (deemed to be University),
Mangalore, India.
Correspondence to: Dr Rathika D Objective: To assess the effect of maternal occupational tobacco handling (bidi rolling) on
Shenoy, Professor and Head, Depart- cord serum leptin levels. Methods: We enrolled 64 neonates born to women who were
ment of Pediatrics, KS Hegde Medical bidi-rollers, and 64 small for gestational age (SGA) neonates and 57 term appropriate for
gestational age (AGA) neonates born to mothers with no tobacco exposure. Cord blood
Academy, Nitte (deemed to be Univer-
leptin levels between the groups were compared. Adjusted mean difference in leptin was
sity), Mangalore, India. calculated using regression model. Results: Cord leptin showed moderate correlation with
rathika.shenoy@nitte.edu.in birthweight (r=0.16; P=0.027) across the groups. Mean (SD) cord serum leptin levels (ng/
Received: April 09, 2020; mL) of study group was 19.79 (13.32), in comparison to 21.4 (13.4) of SGA (P=0.497), and
Initial review: April 20, 2020; 27.70 (13.96) of term AGA (P=0.002). Maternal occupational tobacco exposure contributed
Accepted: August 08, 2020. to significant decrease in cord leptin (adjusted mean difference (95%CI): -4.5 ng/mL (-8.82,
-0.19); P=0.041). Conclusion: Maternal occupational tobacco exposure causes signifi-
cant reduction in fetal leptin levels.
Keywords: Barker hypothesis, Bidi-rolling, Cotinine, Nicotine, Small for gestational age.
F
etal growth is determined by the integrity of the September, 2019) after institutional ethics committee
utero-placental unit and fetal adipokine axis. The clearance. The group of interest were 64 neonates born to
Barker theory on the role of leptin in initiating the bidi rollers by occupation (Group I). Controls were 64
fetal-programming cascade in small for gestational SGA (Group II) and 57 term appropriate for gestational age
age (SGA) neonates has been of interest for decades [1]. (AGA) newborns (Group III) with no maternal occupatio-
Leptin secreted by the placenta and fetal adipose tissue is nal tobacco exposure or history of smoking. Group II and
important in maintaining energy homeostasis [2]. Leptin Group III newborns were included subsequent to
has positive correlation with birth weight independent of enrolment of each Group I newborn. Infants born to
other maternal factors [3,4]. Smoking during pregnancy mothers exposed to any other form of tobacco exposure
causes placental insufficiency and fetal neuro-endocrine like snuff, chewing, passive and active smoking were
dysfunction resulting in SGA neonates [5]. Studies show excluded in all. Multiple gestations, maternal pre-existing
normal [6-10] to decreased [3,4] cord serum leptin in term systemic illnesses, early preterm (<32 weeks), very low
and preterm infants born to mothers who smoke, birthweight, and newborns with major congenital
independent of birthweight. anomalies were also excluded.
Bidi-rolling is another form of tobacco exposure. Mothers were interviewed for bidi rolling practices.
Coastal Karnataka is home to bidi industry and women Co-variates included pre-pregnancy body mass index
constitute the major labor pool involved in rolling and (BMI), weight gain, anemia, gestational hypertension
packaging [11]. In a cohort study, we established that (GH), prematurity and neonatal anthropometry. Standard
occupational tobacco exposure through bidi rolling definitions and measurements were used [13]. AGA
resulted in increased relative risk for SGA and a lower was defined as birthweight between the 10th and 90th
adjusted birthweight [12]. We hypothesized that similar to centile and SGA as less than 10th centile in the
maternal smoking, tobacco handling during pregnancy Lubchenco charts [14].
may have an effect on the newborn umbilical cord serum
leptin levels independent of birthweight. Cord serum leptin assay was done for all participants;
maternal and cord serum cotinine assays were performed
METHODS
only in the study group. Both assays were done by
The study was conducted over two years (October, 2017- commercial ELISA kits and expressed as ng/mL. A serum

RAO, ET AL. CORD BLOOD LEPTIN AND MATERNAL TOBACCO EXPOSURE
cotinine value ≥2 ng/mL was considered indicative of tobacco exposure was 6.75 (4,10.75) years. They rolled a
nicotine absorption [15]. Sera were separated and stored median (IQR) of 500 (500,600) bidis a day and majority
at –80°C until analysis. The tests were repeated twice to (84.4%) stopped rolling by median (IQR) 22 (20.5,29.5)
minimize errors. weeks of gestation. Evidence of nicotine absorption was
found in 24 (37.5%) of maternal and 22 (34.4%) of cord
Primary outcome was to assess the effect of maternal
blood. Median (IQR) maternal cotinine was 3.35 (0,15.15)
tobacco handling on cord serum leptin independent of
ng/mL; and median (IQR) cord serum cotinine 4.0 (0,
birthweight and being SGA. Secondary outcome was to
17.25) ng/mL (range 0-30.45). Cord leptin had significant
look into specific maternal tobacco handling practices
negative correlation with longer years of occupational
that influenced the leptin level.
tobacco handling (r = –0.34; P=0.001) and longer tobacco
Sample size calculated was 57 in each group using exposure (gestational week) during pregnancy (r = –0.33;
online software OpenEpiv3 for 90% confidence level, 20% P=0.007). There was no correlation between cord leptin,
allowable error, 1:2 ratio of study to control groups and maternal cotinine and cord cotinine.
mean difference in cord serum leptin of 1.04 ng/mL [4]. Maternal occupational tobacco exposure contributed
Informed written consents were obtained from the to significant decrease in cord leptin by 4.50 ng/mL
participating women. [95%CI: –8.82, –0.19; P=0.041] when adjusted for maternal
Statistical analyses: These were performed using SPSS gestational hypertension, prematurity and birthweight.
v20.0. For categorical data, frequencies (n) and percen- Bidi rolling practices associated with decrease in cord
tages (%) were calculated and Chi square or Fisher exact leptin value included longer years of occupational
was applied for significance. For continuous data, either exposure [aMD (95%CI): –1.31 (–2.22, –0.41); P=0.005]
mean (SD) or median (IQR) was calculated based on and longer weeks of exposure into pregnancy [aMD
normality distribution. Intergroup comparisons were (95%CI): –0.72 (–1.35, –0.09); P=0.025] when adjusted for
performed using independent sample t test or ANOVA. number of bidis rolled in a day, quantity of tobacco stored
Correlation was done by Pearson correlation or Spearman at home and engagement of other family members in the
correlation test. Multiple linear regression model was same occupation.
used to determine adjusted mean difference (aMD) of DISCUSSION
cord leptin for maternal tobacco exposure. A P value less
In our study, the cord serum leptin levels of the newborns
than 0.05 was considered significant.
born to mothers who were bidi rollers were significantly
RESULTS
Of the 64 mothers with occupational tobacco exposure, 16 Table I Comparison of Maternal and Neonatal Variables
(25%) were SGA. Other maternal and newborn Among the Study Groups
characteristics that influenced the birth weight and/or the Variable Group I Group II Group III
cord serum leptin levels are given in Table I. Cord serum (n=64) (n=64) (n=57)
leptin showed moderate correlation with birthweight Maternal
(r=0.16; P=0.027) across the groups, with no difference
Age, y 28.3 (4.03) 27.3 (4.5) 26.9 (4.01)
between females (n=92) 23.25 (12.78) ng/mL and males
(n=93) 22.10 (14.90) ng/mL (P=0.58). BMI, kg/m2 21.7 (3.6) 21.8 (2.8) 22.7 (1.9)
Weight gain, kg$ 9.96 (2.71) 8.23 (1.80) 9.5 (2.30)
As compared to group III (term AGA with no maternal Hemoglobin, g/dL 11.6 (1.2) 11.6 (1.2) 11.9 (0.9)
tobacco exposure), cord serum leptin levels were signifi-
Newborn
cantly lower in group I (maternal tobacco exposure)
[Mean difference (95% CI)= –7.91 (–12.92,–2.90); Gestational age, wk 38.2 (1.3) 37.9 (1.2) 38.4 (0.9)
P=0.002] and group II (SGA with no maternal tobacco Birthweight, g* 2829.4 2355.9 3213.9
exposure) [MD (95% CI) = –6.30 (–11.33, –1.28); P=0.014]; (374.3) (182.9) (300.2)
even term AGA newborns of group I had significantly Length, cm* 48.6 (1.88) 47.2 (1.44) 49.3 (1.99)
lower levels than term AGA newborns of group III [MD HC,cm* 33.7 (1.13) 32.5 (1.06) 33.8 (0.8)
(95% CI) = –8.5 (–13.89, –3.11); P=0.002]. No significant Leptin, ng/mL^# 19.79 (13.31) 21.4 (13.40) 27.7 (13.96)
difference was found between the levels in group I and All values in mean (SD); Group I: Maternal Tobacco Exposure,
group II (P=0.49). Group II: Small for gestational age without tobacco exposure,
Group III: Term Appropriate for gestational age without tobacco
Mothers in the study group started bidi rolling at exposure; HC-head circumference; BMI-body mass index; $Preg-
median (IQR) age of 20 (18,23) years. Their median (IQR) nancy weight gain; #P=0.005. *P<0.001;^cord serum leptin.


• Bidi rolling during pregnancy reduces the cord blood leptin levels independent of birthweight and being born
small for gestational age.
lower when compared to those born to the reference Mufeeda Alungal and Dr Arun Varghese for their help in data and
group. Mantzoros, et al. [4] documented that the cord blood collection.
decrease in mean cord leptin in pregnant smokers was Ethical clearance: Institutional ethics committee, K S Hegde
more pronounced in preterm neonates. A significant Medical Academy; No. INST.EC/EC/53/2017-18, dated March
23, 2017.
negative correlation between cord leptin and number of
Contributors: SSR, RDS: conceived and designed the study,
cigarettes smoked has also been reported [4,8]; though, involved in data analysis and writing the manuscript; AP, YSK:
Kayemba-Kay, et al. [3] showed a positive correlation. contributed in sample collection and conducted laboratory
Fang, et al. [7] noted that the median cord leptin investigations. DMY contributed in data collection. All the
concentration in smokers was less than that of the non- authors were involved in critical appraisal of the manuscript.
smokers. Funding: Nitte deemed to be university Faculty research grant.
Competing interest: None stated.
Nicotine influences cord leptin through decreased
secretion due to uteroplacental insufficiency, decreased REFERENCES
birthweight and catecholamine-mediated decreased fetal 1. Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C.
adiposity [4]. In the present study, longer the years of Relatively low serum leptin levels in adults born with intra-
tobacco exposure and longer the mother continued with uterine growth retardation. Int J Obes Relat Metab Disord.
her occupation into pregnancy, lower was the cord leptin. 2001;25:491-5.
The lower age in most women in this study substantiates 2. Briffa JF, McAinch AJ, Romano T, Wlodek ME, Hryciw
that they begin this occupation in late adolescence, DH. Leptin in pregnancy and development: A contributor
to adulthood disease? Am J Physiol Endocrinol Metab.
unwittingly helping their mothers [11]. The cord blood
2015;308:e335-50.
leptin level of the tobacco exposed newborns was 3. Kayemba-Kay’s S, Geary MPP, Pringle J, Rodeck CH,
comparable to the unexposed SGA babies. This indicated Kingdom JCP, Hindmarsh PC. Gender, smoking during
that these newborns with in utero tobacco exposure had pregnancy and gestational age influence cord leptin concen-
an adiposity similar to that of an SGA newborn in spite of trations in newborn infants. Eur J Endocrinol. 2008; 159:
being born AGA. It also suggested a common 217-24.
pathophysiology compromising the circulation of the 4. Mantzoros CS, Varvarigou A, Kaklamani VG, Beratis NG,
growing fetus in both. Maternal malnutrition may be an Flier JS. Effect of birth weight and maternal smoking on
additional factor common to both the groups [2]. cord blood leptin concentrations of full-term and preterm
newborns. J Clin Endocrinol Metab. 1997;82:2856-61.
This was a single centre study with a small sample 5. National Center for Chronic Disease Prevention and Health
size. Nicotine absorption was demonstrable only in about Promotion (US) Office on Smoking and Health. The Health
one-third, probably related to altered metabolism kinetics Consequences of Smoking – 50 Years of Progress: A Report
during pregnancy [12,15]. There is wide variation in of the Surgeon General [Internet]. Atlanta (GA): Centers
for Disease Control and Prevention (US); 2014. Available
reported cord leptin values with several maternal, labour
from: http://www.ncbi.nlm.nih.gov/books/NBK179276/.
and newborn factors influencing the same [7,16]. We Accessed January 27, 2020.
included two control population of newborns and 6. Fleisch AF, Rifas-Shiman SL, Rokoff LB, Hivert M,
statistically adjusted various covariates that could Mantzoros CS, Oken E. Associations of maternal prenatal
influence cord leptin levels. Future considerations smoking with umbilical cord blood hormones: The Project
include a longitudinal study with other fetal hormones in Viva Cohort. Metabolism. 2017;72:18-26.
newborns with maternal occupational tobacco exposure. 7. Fang F, Luo ZC, Dejemli A, Delvin E, Zhang J. Maternal
smoking and metabolic health biomarkers in newborns.
In conclusion, maternal occupational exposure to PLoS One. 2015;10:e0143660.
tobacco via bidi rolling decreases cord serum leptin 8. Chelchowska M, Ambroszkiewicz J, Mazur J, Lewan-
independent of birthweight and being SGA. Maternal dowski L, Maciejewski TM, Oltarzewski M, et al. Effect of
bidi rolling is a demographic risk factor for altered tobacco smoking on the maternal and fetal adipokine axis in
neuroendocrine function of the fetus. relation to newborn birth weight and length. Przegl Lek.
2014;71:567-71.
Acknowledgements: Dr P Nayan Baba, Dr B Balakrshina, Dr 9. Pardo IM, Geloneze B, Tambascia MA, Barros-Filho AA.

Does maternal smoking influence leptin levels in term, 13. American College of Obstetricians and Gynecologists;
appropriate-for-gestational-age newborns? J Matern Fetal Task Force on Hypertension in Pregnancy. Hypertension
Neonatal Med. 2004;15:408-10. in pregnancy. Report of the American College of Obstetri-
10. Helland IB, Reseland JE, Saugstad OD, Drevon CA. cians and Gynecologists’ Task Force on Hypertension in
Smoking related to plasma leptin concentration in pregnant Pregnancy. Obstet Gynecol. 2013;122(5): 1122-31.
women and their newborn infants. Acta Paediatr. 14. Lubchenco LO, Hansman C, Boyd E. Intrauterine growth in
2001;90:282-7. length and head circumference as estimated from live births
11. International Labour Organisation. Making ends meet: Bidi at gestational ages from 26 to 42 weeks. Pediatrics. 1966;
workers in India today. Study of four states. Geneva: 37:403-8.
International Labour Organisation; 2003. Available from: 15. Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine
http://www.ilo.org/public/english/dialogue/sector/papers/ chemistry, metabolism, kinetics and biomarkers. Handb
food/ wp202.pdf. Accessed Jan 25, 2020. Exp Pharmacol. 2009;192:29 60.
12. Shenoy RD, Sindgikar SP, Shenoy V, Uppoor R, Rao R, 16. Stefaniak M, Dmoch-Gajzlerska E, Mazurkiewicz B,
Singh S. Pregnancy outcome in occupational tobacco Gajzlerska-Majewska W. Maternal serum and cord blood
exposure: A cohort study from South India. Indian J leptin concentrations at delivery. PLoS One. 2019;14:
Community Med. 2020;45:54-9. e0224863.
ADVERTISEMENT
INDIAN JOURNAL OF PRACTICAL PEDIATRICS
Quarterly Subscription Journal of IAP publishing review articles

useful for PG students and practitioners as ready reckoner
Forthcoming issues for the year 2020 (Vol.22)
Vol 22. No. 4. Vaccinology

Science and practice of vaccine scheduling, VPD Surveillance, Medico legal issues in immunization,
Cold chain – Maintenance and monitoring, Vaccines in special situations, AEFI – Prevention, monitoring
and reporting, DTP vaccines plus, Polio vaccines – Issues, COVID 19 Vaccines – Update, CNS Vaccines,
Influenza vaccines – Indian context, FAQs in immunization, Pneumococcal vaccines, Immunology of
vaccines, Rota virus vaccines.
SUBSCRIPTION TARIFF
Individual Annual 750 Institution Annual 4,000
10 years 6,500 Five years 16,000
Foreign Annual US $ 75
Payment details
• Pay through DD: Send your crossed demand draft, drawn in favour of INDIAN JOURNAL OF
PRACTICAL PEDIATRICS, payable at Chennai to IJPP Office
• Pay online: www.ijpp.in
• Pay through online transfer, find below bank details
Bank Name: THE KARUR VYSYA BANK Account Name: Indian Journal of Practical Pediatrics
Account Number:1154115000004720 IFSC code: KVBL0001878
JOURNAL OFFICE:
DR. S.THANGAVELU, Editor-in-Chief,1A, Block II, Krsna Apartments, 50, Tamil Salai
(Halls Road), Egmore, Chennai - 600 008, Tamilnadu, India.
Phone: +91-44-28190032, 42052900. Email: ijpp_iap@rediffmail.com

RESEARCH PAPER
Role of Flexible Bronchoscopy in Ventilator-Dependent Neonates

JAVEED IQBAL BHAT,1 BASHIR A CHAROO,1 SHIHAB ZAHOOR,1 QAZI IQBAL AHMAD1 AND AMBREEN ALI AHANGAR2
From the Department of 1Pediatrics Sher-i-Kashmir Institute of Medical Sciences; and Department of 2Anesthesia, Government
Medical College; Srinagar, Jammu and Kashmir, India.
Correspondence to: Dr Javeed Iqbal Objective: To assess the usefulness and safety of flexible bronchoscopy in ventilated
Bhat, Department of Pediatrics, neonates with extubation failure. Method: This was a prospective observational study.
SKIMS, Soura, Jammu and Kashmir, Flexible bronchoscopy was done in eligible patients with failure of extubation form invasive
ventilation. The main outcome measure was to find the presence of any anatomic or
India. drjaveediqbal@gmail.com
dynamic abnormalities of the airways of these patients and the organism profile of
Received: January 17, 2019; bronchoalveolar lavage (BAL) fluid. Results: Forty-eight babies (68.8% preterm) were
Initial review: June 07, 2019; enrolled in the study. The most common finding on bronchoscopy was airway edema seen in
Accepted: August 14, 2020. 13 (27%) patients. BAL culture was positive in 29 (74%) patients. Overall treatment was
modified in 35 (73%) patients based on bronchoscopy findings/BAL culture. Majority of
infants (83.3%) tolerated the procedure very well. Conclusion: Flexible bronchoscopy
provides useful information in the management of newborn babies with extubation failure.
Keywords: Bronchoalveolar lavage, Extubation failure, Management, Preterm.
P
rolonged ventilation may lead to multiple May, 2014 to April, 2018 at a tertiary-care public hospital
adverse effects, including subglottic stenosis, of India. The study participants were neonates with a
tracheobronchomalacia, nosocomial infection, gestational age of more than 32 weeks and failure of
bronchopulmonary dysplasia (BPD) and neuro- extubation (defined by a need for re-intubation within 48
cognitive impairment [1-3]. Up to 30% of mechanically hours of extubation). Eligibility for and benefit of
ventilated infants require a prolonged period of invasive bronchoscopy were determined by the attending
mechanical ventilation and experience repeated neonatologists. Written informed consent was taken from
extubation failures. Kurachek, et al. [5], in their study on parents/legal guardians before undertaking the proce-
pediatric patients, reported that upper airway obstruction dure. The study was approved by the institutional ethical
like subglottic stenosis, laryngo-malacia, tracheomalacia committee.
are the leading causes of extubation failure [EF]. These
Flexible bronchoscopy was done in the neonatal
observations demand prompt and precise diagnosis of
intensive care unit (NICU) or bronchoscopy suite, which
these conditions. Similarly, ventilator-associated pneu-
is in close proximity to neonatal ICU. The bronchoscopy
monia (VAP) also increases the duration of mechanical
team comprised of a bronchoscopist, bronchoscopy
ventilation.
technologist, neonatologist, pediatric resident doctor
Flexible bronchoscopy is a well-established tool for and a nurse. Stable ventilated neonates were extubated
the evaluation of airway anomalies and infections in for the duration of the procedure in order to check for any
neonatal ICU, with excellent safety profile [6]. Moreover, upper airway anatomic and dynamic abnormality. Pre-
therapeutic interventions with flexible bronchoscopy like oxygenation to ensure oxygen saturation remained above
mucus plug removal, can efficiently relieve airway 90% was carried out. The majority of bronchoscopies
problems and can decrease the duration of ventilation were performed trans-nasally, the trans-oral route was
[7,8]. There is a paucity of literature regarding the role of used in four patients (cleft palate in two patients, choanal
flexible bronchoscopy in prolonged mechanical stenosis in one patient and epistaxis in one patient). In 10
ventilation/failure of extubation in neonates. We studied patients, bronchoscopy was done via an endotracheal
the utility and safety of this modality in neonates on tube with a tube size of 3.5 mm, because of high ventilator
prolonged ventilation/extubation failure. settings. Extubation was also attempted at some point in
time in this sub-group. Upper airway could not be
METHODS
assessed in this subgroup. This subgroup consisted of
We provide data on neonatal flexible bronchoscopy from six-term babies and four late preterm babies. The authors

BHAT, ET AL. BRONCHOSCOPY IN VENTILATED NEONATES
used Olympus BF-XP160F (Olympus Corporation, Japan) and 2.5 (0.67) kg, and the median (IQR) chronological age
scope with an outer diameter of 2.8 mm and a channel size at which procedure was done was 15 (9.25,20.75) days.
of 1.2 mm. Electrocardiogram and pulse were recorded Three patients were classified as chronic lung disease at
continuously during the procedure and non-invasive the time of inclusion in the study. Ventilator-associated
blood pressure was monitored every 3-5 minutes. pneumonia (VAP) was diagnosed in 24 (50%) ventilator-
Supplemental oxygen was given via nasal cannula. dependent patients prior to bronchoscopy. Persistent
Desaturation ≤90% was managed by an increase in lobar atelectasis was seen in 12 ventilator-dependent
oxygen flow rate and the use of an oxygen mask. 2% patients and bronchoscopy was done with diagnostic
lidocaine gel was used locally to anesthetize nasal and therapeutic intent (removal of possible mucus plug).
mucosa. 1 mL aliquots of 2% lidocaine in 1:1 dilution with Respiratory distress syndrome (RDS) was the most
normal saline were instilled by the ‘spray-as-you- common reason for mechanical ventilation [20], followed
go’ technique. Additional doses were given, if required, by post-surgery [7] and meconium aspiration syndrome
to minimize patient discomfort. Bronchoalveolar lavage [6].
(BAL) was performed with the use of normal saline
Table I shows bronchoscopy findings and organism
warmed to body temperature with a volume of 3 mL/kg
profile of bronchoalveolar lavage culture. Bronchoscopy
administered in three divided doses. The bronchoscope
evaluations revealed airway abnormalities in 38 (79%)
was advanced until wedged in a desired subsegmental
patients – more than one abnormality was found in 24
bronchus; this technique ensured the collection of a
(50%). The most common finding was airway edema seen
sample from the terminal airways with negligible
in 13 (27%) patients. Laryngomalacia/ tracheomalacia or
contamination from the upper airways. It was sent for
bronchomalacia was seen in 25 (52%) of patients. Bron-
gram staining, lipid-laden macrophages, bacterial culture,
choalveolar lavage was done in 39 patients, with
and fungal culture. Bronchoscopy findings were noted if
adequate BAL sample collected in all. BAL culture was
present. Tracheobronchial abnormalities recorded
positive in 29 (74%) patients; the most common organism
included subglottic stenosis, tracheomalacia (tracheo-
isolated was Acinetobacter baumannii.
malacia or bronchomalacia was diagnosed when there
was a 50% reduction in the luminal diameter during Overall treatment was modified in 35 (73%) patients
expiration), tracheal stenosis, complete tracheal rings, based on bronchoscopy findings/BAL culture, including
tracheoesophageal fistulas, vascular rings, broncho- tracheostomy in five patients (3, subglottic stenosis; 1,
malacia, hemangiomas, or mucus plugging. Therapeutic subglottic hemangioma; 1, severe tracheomalacia). Laser
procedures carried out were also noted. BAL culture was excision of subglottic stenosis through rigid
done by using the BacT/Alert automatic culture system. bronchoscopy was done in two patients, successful
Culture results including organism profile and culture
sensitivity were recorded. Table I Bronchoscopy and Bronchoalveolar Lavage Findings
in Ventilator-Dependent Neonates (N=48)
A standardized data extraction form was used to
obtain the demographic and clinical data including Findings* No. (%)
patient age, sex, weight, co-morbidities, procedure Airway edema 13 (27)
indication, total midazolam dose, pulse rate, baseline and Tracheomalacia 10 (20.8)
lowest blood pressure, oxygen saturation, adverse
Laryngomalacia 8 (16.6)
events if any during and/or within one hour of the
procedure. Mucus plug 8 (16.6)
Bronchomalacia 7 (14.5)
Statistical analysis: It was performed using SPSS 20.0.
Subglottic stenosis 5 (10.4)
The normality of the data was checked by using the
Shapiro- Wilk test. Categorical variables are presented as BAL fluid culture
percentages and continuous data as mean (SD)/median A. baumannii 11 (22.9)
(IQR). K. pneumoniae 10 (20.8)
P. aeruginosa 4 (8.3)
RESULTS
S. aureus 2 (4.1)
During the study period, 998 newborn babies received E. coli 1 (2.0)
mechanical ventilation for different indications; 48 of
C. albicans 1 (2.0)
these (68.8% preterm) underwent flexible bronchoscopy
with or without BAL. The mean (SD) gestational age and *Subglottic hemangioma, H-type fistula, right bronchial agenesis,
vascular ring, and choanal stenosis in one neonate each; BAL
birthweight of the study population was 36.4 (2.2) weeks bronchoalveolar fluid.


• Flexible bronchoscopy is a useful intervention in select neonates with extubation failure.
mucus plug removal for atelectasis in five patients with extubation failure in ELBW infants, atelectasis was also
mucus plug (post-bronchoscopy X-ray (n=3) showed found as one of the causes of extubation failure.
persistent collapse of affected lobe), placement of oral Extubation failure due to airway complications involving
airway for choanal stenosis in one patient, surgical glottic, subglottic, or tracheobronchial pathology is well
procedure for H type fistula in one patient, and reported in the literature [15].
modification of antibiotics based on BAL culture in 21
patients. Overall 31 (64%) patients were successfully The study has some limitations. This is a review of
extubated within a week of the bronchoscopy procedure, records with no control group, and no standardization
and 39 (81.5%) patients could be extubated within 14 days regarding the definition of prolonged mechanical
of the procedure. ventilation; the decision for bronchoscopy was based on
the clinical experience of the attending neonatologist.
Procedural complications like transient hypoxia (n=4), Secondly, the sample size is small and this was a single-
bradycardia (n=2), transient apnea (n=1) and epistaxis center study.
(n=1) were seen in 8 (16.7%) patients.
To conclude, flexible bronchoscopy can be incor-
DISCUSSION porated as a diagnostic and therapeutic modality in
We found flexible bronchoscopy to be a useful diagnostic newborn babies with extubation failure, and we can get
and therapeutic tool in babies on prolonged mechanical useful information about the cause of extubation failure.
ventilation. Bronchoscopy evaluations revealed airway Ethics clearance: Departmental Review Board, SIMS; No. SIMS/
abnormalities in a significant number of our patients. 152/12/279; dated June 2, 2016.
More than half of the subjects (25/48) had laryngo- Contributors: JIB, BAC: conceived the idea of the study and
malacia, tracheomalacia, or bronchomalacia, which was writing the manuscript; SZ: was involved in management and
likely due to bronchopulmonary dysplasia and/or chronic data collection; QIA: supervised implementation of the study;
mechanical ventilation, which are known to cause AAA: contributed to writing of the manuscript. All authors
tracheobronchomalacia [9]. Flexible broncho-scopy approved the final version of manuscript, and are accountable for
all aspects related to the study.
helped us to modify treatment in 73% of ventilator-
dependent neonates based on the bronchoscopic/BAL
culture findings. REFERENCES
A 7-year retrospective study on 599 neonates who 1. Sant’Anna GM, Keszler M. Weaning infants from
underwent flexible bronchoscopy reported its importance mechanical ventilation. Clin Perinatol. 2012;39:543-62.
as a diagnostic and therapeutic tool in the management of 2. Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright
neonatal lung disease, Vijayasekaran, et al. [10] reported LL, Fanaroff AA, et al. Validation of the national institutes
neonatal bronchoscopy safe in experienced hands and of health consensus definition of bronchopulmonary
dysplasia. Pediatrics. 2005;116:1353-60.
invaluable tools in the management of a neonate with
3. Walsh MC, Morris BH, Wrage LA, Vohr BR, Poole WK,
various respiratory disorders. Others have also provided Tyson JE, et al. Extremely low birthweight neonates with
similar conclusions [6]. The most important factor respon- protracted ventilation: Mortality and 18-month neuro-
sible for ventilator dependence is ventilator-associated developmental outcomes. J Pediatr. 2005;146:798-804.
pneumonia [11]. Chest X-ray has poor sensitivity to 4. Currie A, Patel DS, Rafferty GF, Greenough A. Prediction
diagnose VAP because the presence of pulmonary of extubation outcome in infants using the tension time
infiltrates on chest X-ray is one of the main criteria for index. Arch Dis Child Fetal Neonatal Ed. 2011;96:F265-9.
diagnosing VAP, which may also be caused by other 5. Kurachek SC, Newth CJ, Quasney MW, Rice T, Sachdeva
conditions like pulmonary edema, atelectasis or RC, Patel NR, et al. Extubation failure in pediatric intensive
care: A multiple-center study of risk factors and outcomes.
pulmonary hemorrhage [11]. Similarly, culture of the
Crit Care Med. 2003;31:2657-64.
tracheal aspirate has a high chance of contamination with 6. Hysinger E, Friedman N, Jensen E, Zhang H, Piccione J.
colonizing microorganisms [12]. BAL microbiology is a Bronchoscopy in neonates with severe bronchopulmonary
very good marker for the diagnosis of lung infection [13]. dysplasia in the NICU. J Perinatol. 2019;39:263-8.
In a study by Wang, et al. [14] on risk factors of 7. Bar-Zohar D, Sivan Y. The yield of flexible fiberoptic

bronchoscopy in pediatric intensive care patients. Chest. lung disease: A wakeup call. Lung India. 2014;31:1-3.
2004;126:1353-9 12. De Blic J, Midulla F, Barbato A, Clement A, Dab I, Eber E,
8. Lin YT, Lee YS, Jeng MJ, Chen WY, Tsao PC, Chan IC, et et al. Bronchoalveolar lavage in children. ERS task force on
al. Flexible bronchoscopic findings and the relationship to bronchoalveolar lavage in children. European Respiratory
repeated extubation failure in critical children. J Chin Med Society. Eur Respir J. 2000;15:217-31.
Assoc. 2018;81:804-10. 13. Bhat JI, Wani WA, Ahmad QI, Charoo BA, Ali SW,
9. Downing GJ, Kilbride HW. Evaluation of airway Ahangar AA, et al. Flexible bronchoscopy in non-resolving
complications in high-risk preterm infants: Application of pneumonia. Indian J Pediatr. 2017;84:681-4.
flexible fiberoptic airway endoscopy. Pediatrics. 1995;95: 14. Wang SH, Liou JY, Chen CY, Chou HC, Hsieh WS, Tsao
567-72. PN. Risk factors for extubation failure in extremely low
10. Vijayasekaran D, Kalpana S, Ramachandran P, birth weight infants. Pediatr Neonatol. 2017;58:145-50.
Nedunchelian K. Indications and outcome of flexible 15. Walner DL, Loewen MS, Kimura RE. Neonatal subglottic
bronchoscopy in neonates. Indian J Pediatr. 2012;79:1181-4. stenosis-incidence and trends. Laryngoscope. 2001;111:
11. Saydain G. Ventilator-associated pneumonia in advanced 48-51.
ADVERTISEMENT

RESEARCH PAPER
Validation of the Testicular Workup for Ischemia and Suspected Torsion

(TWIST) Score in the Diagnosis of Testicular Torsion in Children With
Acute Scrotum
PRADYUMNA PAN
From Pediatric Surgery Unit, Ashish Hospital and Research Centre, Jabalpur, Madhya Pradesh, India.
Correspondence to: Dr Pradyumna Objective: To validate the Testicular Workup for Ischemia and Suspected Torsion (TWIST)
Pan, Pediatric Surgery Unit, Ashish score for the evaluation of children presenting with acute scrotum. Methods: This
Hospital and Research Centre, prospective study calculated TWIST score in patients of acute scrotum admitted to a
pediatric surgery unit. The scoring system consisted of testicular swelling (2 points), hard
Jabalpur, Madhya Pradesh, India.
testicle (2), absent cremasteric reflex (1), nausea/vomiting (1) and high-riding testis (1). All
dr_pan@rediffmail.com the patients were examined by a pediatric surgeon. Results: Among 96 children with acute
Received: November 04, 2019; scrotum, 68 (70.8%) patients had testicular torsion. In the testicular torsion group, the mean
Initial review: January 23, 2020; (SD) TWIST score was 5.7 (1.2) and in no torsion group, it was 1.46 (0.67). In the testicular
Accepted: August 22, 2020 torsion group, the number of patients with low, intermediate, and high risk was 0, 13, and 55,
respectively and in without testicular torsion these were 21, 7, and 0, respectively.
Conclusions: TWIST score has high predictive value for testicular torsion, and can be
used for clinical diagnosis of testicular torsion.
Keywords: Color doppler, Management, Orchidectomy, Spermatic cord torsion.
T
esticular torsion is the most common pediatric years (May, 2017 to April, 2019) in a tertiary referral centre.
urological emergency, affecting 3.8 per 100,000 Institutional review board and ethical committee approval
males younger than 18 years annually [1]. were obtained. Participants included were males aged 0
Around 10-5% of these are children with acute days to 18 years, presenting to ER with chief complaint of
scrotal disease [2], and results in a 42% orchiectomy rate testicular pain and/or swelling. Patients were excluded if
for boys undergoing testicular torsion surgery. Testicular their pain was due to trauma, if symptoms were present for
salvage requires timely detection and treatment, and greater than one week, there was a history of testicular
torsion should be excluded in all patients with acute disease or surgery, and if a diagnosis of testicular torsion
scrotum. Doppler ultrasound (DUS) has been considered had already been confirmed or excluded.
as the primary imaging method for the assessment of
The TWIST score is based on the sum (ranging from 0
testicular torsion with high sensitivity and specificity [3].
to 7) of the following findings: testicular swelling (2
However, for those with testicular torsion, the use of DUS
points), hard testicle (2 points), absent cremasteric reflex
can prolong the time in testicular ischemia and delay
(1 point), nausea or vomiting (1 point), and high riding
surgery. The availability of radiological imaging and the
testicle (1 point) [4]. The risk stratifying scores for those
expertise of its operators and evaluators are also limited in
at low risk for testicular torsion is 0 to 2 points, inter-
many settings. Barbosa, et al. [4] developed a Testicular
mediate risk was 3 to 4 points, and high risk for testicular
Workup for Ischemia and Suspected Torsion (TWIST)
torsion is 5 to 7 points [4]. The primary conclusion was a
score based on clinical parameters [4]. Typically, there is a
diagnosis of testicular torsion by TWIST score, con-
4-8 hour window before permanent ischemic damage to
firmed by surgical exploration as the final diagnosis.
testes occurs. Treatment delays may be associated with
Testicular loss was defined as either surgical orchiectomy
reduced fertility or may require orchiectomy. The purpose
or determination of significant atrophy at 6 months post-
of this study is to study the utility of the TWIST scoring
operative ultrasound. A more than 50% difference in
system for testicular torsion in boys presenting to the
volume compared with the contralateral testis or absence
emergency room (ER) with an acute scrotum.
of blood flow on Doppler was considered to represent
METHODS testicular loss [5].
This observational study was carried over a period of two The TWIST score was performed by a single pediatric

PRADYUMNA PAN TWIST SCORE IN TESTICULAR TORSION
surgeon in all patients, and surgery was carried out by the Table II Testicular Workup for Ischemia and Suspected
same surgeon. The same sonologist did the DUS Torsion (TWIST) Score in Children With Acute Scrotum
evaluation in all patients. Indication of surgery was (N=96)
impaired blood flow in DUS, and inability to rule out Risk group Twist Testicular No testicular
testicular torsion in the presence of intermediate TWIST score torsion (n=68) torsion (n=28)
score. All patients for whom surgery was indicated
Low 0-2 0 21 (75)
were immediately transferred to the operating room
Intermediate 3-4 13 (19.2) 7 (25)
for scrotal exploration. All patients who underwent
surgical exploration had confirmed diagnoses of High 5-7 55 (80.8) 0
testicular torsion. All values in no. (%).
RESULTS
A cohort of 96 males with acute scrotum was studied. DISCUSSION

The mean age of the patients in the study group was This current study validates the TWIST score, which risk
10.1 (3.8) years (range 1 month-16 year). The TWIST stratifies patients presenting with an acute scrotum for
score component and other clinical features are shown in testicular torsion. There were no patients with torsion in
Table I. the low-risk category (0-2 twist score), and 100% of
In the testicular torsion group, the mean TWIST score patients in the high-risk category (5-7 twist score) had
was 5.7 (1.2 ) (range 3-7), and in no torsion group, it was torsion. In this analysis, the TWIST score was found to
1.46 (0.67 ) (range 0-4). In testicular torsion group, the be an excellent diagnostic tool in the diagnosis of
number of patients with low, intermediate, and high risk testicular torsion, which is comparable to other studies
was 0, 13, and 55, respectively, while the number of [4,6,7]. In this study, all low-risk and high-risk patients
patients without testicular torsion was 21, 7, and 0 in low, (73.9 %) could have avoided the use of an ultrasound
intermediate, and high-risk groups, respectively (Table scan.
II). Doppler ultrasound was obtained in all study
subjects, which diagnosed testicular torsion in 65
patients. Three patients had equivocal ultrasound, Acute scrotum (N=96)
showing no definite torsion with a lack of vascular flow,
and neither increased blood flow to the epididymis. These ↓
Emergency room
patients were surgically proven to have testicular torsion
on exploration. Thus, 68 (70.8%) patients were found to Call Sent to
have testicular torsion. The 6-month follow-up DUS
showed 46 equal sized and normal blood flow testes on ↓ ↓
Pediatric surgeon
both sides, with a salvage rate of 67.6% (Fig. 1). Sonologist
Shifted to preoperative
room and treatment
Opeartion theatre
started
Anesthetist
Table I Clinical Features of Children With Acute Scrotum ↓
(N=96) TWIST Score
Doppler USG
Characteristic Torsion Non torsion
(n=68) (n=28)
Testicular pain 65 (95.6) 26 (92.9) ↓ ↓
Testicular torsion Testicular torsion
Nausea and vomiting 65 (95.6) 26 (92.9) (n=68) absent (n=28)
Abdominal pain 21 (30.9) 9 (32.2)
Tenderness 29 (42.7) 7 (25.0)
↓ ↓
Taken for Shifted to
Testicular swelling 27 (39.7) 7 (25.0) surgery inpatient
High riding testes 55 (80.9) 0 area
↓ ↓
Absent cremasteric reflex 65 (95.6) 0 Salvaged Non-salvaged
Hard testicle 41 (60.3) 6 (21.4) (n=46) (n=22)
Erythema 16 (23.5) 1 (3.6)

Fig. 1 Flowchart of patients with acute scrotum enrolled in the
All values in no. (%); *P<0.01, #P<0.01, ‡P=0.02. study.

PRADYUMNA PAN TWIST SCORE IN TESTICULAR TORSION

• TWIST score categorizes the patient with acute scrotum, and may be useful in situations where ultrasound
facility is not available.
The original TWIST study included no patients with toward improving the quality of care. J Urol. 2011;186:
torsion (0/51) in the low-risk category and all 22 patients 2009-13.
with torsion in the high-risk category [4]. Barbosa, et al. 2. McAndrew HF, Pemberton R, Kikiros CS, Gollow I. The
[4] found that only 20% of patients are in the intermediate- incidence and investigation of acute scrotal problems in
children. Pediatr Surg Int. 2002;18:435-37.
risk group and recommended that DUS is required only in
3. Yazbeck S, Patriquin HB. Accuracy of doppler sonography
this group. The testicular torsion scoring systems are in the evaluation of acute conditions of the scrotum in
now being tested in non-urologic medical providers [8] children. J Pediatr Surg.1994;29:1270-72.
and reducing time delays, costs and reliance on DUS [9]. 4. Barbosa JA, Tiseo BC, Barayan GA, Rosman BM,
The TWIST score is intended to categorize patients Torricelli FC, Passerotti CC, et al. Development and initial
requiring an ultrasound. This score is not designed to validation of a scoring system to diagnose testicular torsion
substitute doppler sonography [4]. Sheth, et al. [6] in children. J Urol. 2013;189:1859-64.
assessed TWIST score in non-pediatric surgery-trained 5. Figueroa V, Pippi Salle JL, Braga LH, Romao R, Koyle
emergency room caregivers diagnosing testicular torsion MA, Bagli DJ, et al. Comparative analysis of detorsion
alone versus detorsion and tunica albuginea decompression
and found it equally effective. The absence of cremasteric
(fasciotomy) with tunica vaginalis flap coverage in the
reflex and high riding rotated testes are sufficiently surgical management of prolonged testicular ischemia. J
reliable for the diagnosis of testicular torsion, as also Urol. 2012; 188:1417-22.
reported by other authors [10,11]. 6. Sheth KR, Keays M, Grimsby GM, Granberg CF, Menon
VS, DaJusta DG, et al. Diagnosing testicular torsion before
In this analysis, the main limitations were the small
urological consultation and imaging: Validation of the
number of cases observed. The TWIST score was evalua- TWIST score. J Urol. 2016;195:1870-6.
ted by a single examiner. At least two examiners should 7. Frohlich LC, Darian NP, Cilento BC, Lee LK. Prospective
have perform the physical examination, thus providing validation of clinical score for males presenting with an
information on inter-observer variation. acute scrotum. Acad Emerg Med. 2017;24:1474-82.
8. Afsarlar CE, Ryan SL, Donel E, Baccam TH, Jones B,
In conclusion, this study has demonstrated that the Chandwani B, et al. Standardized process to improve
TWIST score is reliable to identify testicular torsion in patient flow from the emergency room to the operating
patients with acute scrotum. Since this study was room for pediatric patients with testicular torsion. J Pediatr
conducted in one hospital, studies in multiple settings Urol. 2016;12:233-36.
will support the internal validity of this method. 9. Boettcher M, Krebs T, Bergholz R, Wenke K, Aronson D,
Reinshagen K. Clinical and sonographic features predict
Ethics clearance: Institutional Ethics Committee; No. 17/ASH/ testicular torsion in children: A prospective study. BJU
Study 03/2017, dated January 01, 2017. Internat. 2013;112:1201-6.
Contributors: PP: developed the concept and designed the study, 10. Ciftci AO, S ‘enocak ME, Tanyel FC, Büyükpamukçu N.
collected and analyzed the data, drafted the manuscript. Clinical predictors for differential diagnosis of acute
Funding: None; Competing interest: None stated. scrotum. Eur J Pediatr Surg. 2004;14:333-8.
REFERENCES 11. Tariq OA, Mohammed A, Abdelrahman A, Vishwanatha
K, Prem C, Abdulla A, et al. Suspected testicular torsion in
1. Zhao LC, Lautz TB, Meeks JJ, Maizels M. Pediatric children: Diagnostic dilemma and recommendation for a
testicular torsion epidemiology using a national database: lower threshold for initiation of surgical exploration. Res
Incidence, risk of orchiectomy and possible measures Report Urol. 2018;10:241-9.

SPECIAL ARTICLE
Hyperinflammatory Syndrome in Children Associated With COVID-19:

Need for Awareness
CHANDRIKA S BHAT,1 LATIKA GUPTA,2 S BALASUBRAMANIAN,3 SURJIT SINGH4 AND ATHIMALAIPET V RAMANAN5
From 1Pediatric Rheumatology Service, Rainbow Children’s Hospital, Bangalore, Karnataka, India; 2Department of Clinical
Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh India;
3Department of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, Tamil Nadu, India; 4Allergy Immunology Unit,
Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh,
India; and 5Bristol Royal Hospital for Children and Translational Health Sciences, University of Bristol, Bristol, UK.
Correspondence: Dr Chandrika S Bhat, Rainbow Children’s Hospital, Marathahalli, Bengaluru 560 037, Karnataka, India.
The pandemic of COVID-19 initially appeared to cause only a mild illness in children. However, it is now apparent that a small percentage
of children can develop a hyperinflammatory syndrome labeled as Pediatric inflammatory multisystem syndrome - temporally associated
with SARS-CoV-2 (PIMS-TS). Features of this newly recognized condition may include persistent fever, evidence of inflammation, and
single or multi-organ dysfunction in the absence of other known infections. Some of these children may share features of Kawasaki
disease, toxic shock syndrome or cytokine storm syndrome. They can deteriorate rapidly and may need intensive care support as well.
The PCR test is more often negative; although, most of the children have antibodies to SARS-CoV-2. Although the pathogenesis is not
clearly known, immune-mediated injury has been implicated. We herein provide current information on this condition, in order to raise
awareness amongst pediatricians.
Keywords: Kawasaki disease, Macrophage activation syndrome, Multisystem inflammatory syndrome in children and adolescents
temporally related to COVID-19, Pediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS).
Published online: July 15, 2020; PII: S097475591600208
C
hildren younger than 18 years have been inflammatory syndrome in children and adolescents
reported to constitute only a small proportion temporally related to COVID-19 by the World Health
of cases of coronavirus disease (COVID-19). Organization (WHO) [7] and Multisystem inflammatory
Whilst initial reports described an asympto- syndrome in children (MIS-C) associated with COVID-
matic or milder illness in children [1,2], several countries 19 [8] by Centers for Disease Control and prevention
have now noticed a new hyper-inflammatory syndrome (CDC) (Box I). Although little is known about the
affecting a small percentage of children [3]. This epidemiology, cases of PIMS-TS seem to appear few
condition appears to share features with pediatric weeks after the COVID-19 peak in the population. As of
inflammatory diseases such as Kawasaki disease (KD) 13 May, 2020, there were more than 300 cases of
and Toxic shock syndrome (TSS) [4]. suspected PIMS-TS in Europe and North America [3].
With India lagging behind the peak curve, the authors
The first case of classic KD with concurrent COVID-
hypothesize that we may also see a spurt in this illness in
19 in a child was reported from United States [5].
the coming days.
Subsequently, health authorities in the United Kingdom
(UK) issued an alert describing a serious illness requiring CLINICAL FEATURES
intensive care in children. A number of other regions
significantly affected by COVID-19 such as New York, One of the initial reports [9] described a cluster of eight
Italy and France also reported increasing numbers of children with hyperinflammatory shock. Mean age at
children with a similar inflammatory syndrome [3]; the presentation was 8.8 years with a predilection for boys of
first such case was reported from India only recently [6]. Afro-Caribbean descent and seven of these were above
The Royal College of Pediatrics and Child Health the 75th centile for weight. Mean duration of fever at
(RCPCH) published a guidance to raise awareness presentation was 4.3 days. Mucocutaneous changes (rash,
amongst clinicians for this newly recognized condition conjunctivitis, peripheral edema) with significant gastro-
called Pediatric inflammatory multisystem syndrome - intestinal symptoms were noted in all of them. All 8
temporally associated with SARS-CoV-2 (PIMS-TS) [4]. patients developed severe refractory shock with a mean
A similar clinical entity was defined as the Multisystem ferritin level of 1086.6 ng/mL. One child required extra-

BHAT, ET AL. HYPERINFLAMMATORY SYNDROME IN CHILDREN
Box I Proposed Case Definitions for the Hyperinflammatory Syndrome Associated With COVID-19 [4,7,8]
World Health Organization
Children and adolescents 0-19 years of age with fever >3 days
AND two of the following:
(a) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
(b) Hypotension or shock
(c) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings
or elevated Troponin/NT proBNP)
(d) Evidence of coagulopathy (by PT, PTT, elevated D-dimer)
(e) Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)
AND
Elevated markers of inflammation such as ESR, CRP or procalcitonin.
AND
No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock
syndromes.
AND
Evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.
Royal College of Pediatrics and Child Health
A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP and lymphopenia) and evidence
of single or multi-organ dysfunction.
This may include children fulfilling full or partial criteria for Kawasaki disease.
Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes,
infections associated with myocarditis such as enterovirus.
SARS-CoV-2 PCR testing may be positive or negative.
Centers for Disease Control
An individual aged <21 years presenting with fever, laboratory evidence of inflammation and evidence of clinically
severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory,
hematologic, gastrointestinal, dermatologic or neurological)
(i) Fever ≥38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.
(ii) Laboratory evidence (but not limited to) of one or more of the following: an elevated CRP, ESR, fibrinogen,
procalcitonin, D-dimer, ferritin, LDH, or interleukin 6, elevated neutrophils, reduced lymphocytes and low
albumin.
AND
No alternative plausible diagnoses
AND
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; Or COVID-19 exposure
within 4 weeks prior to the onset of symptoms.
CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; LDH: Lactate dehydrogenase.
corporeal membrane oxygenation (ECMO) for refractory were reported from Italy [10] with mean age and duration
shock but eventually died after 6 days of hospitalization. of fever of 7.5 years and 6 days, respectively. Apart from
None of the children had respiratory symptoms and only gastrointestinal and mucocutaneous symptoms, menin-
two tested positive for SARS-CoV-2 PCR, while all of geal signs were also reported in this subset. Half of them
them tested positive for the antibody [9]. Ten children developed KD shock syndrome (KDSS) with peak
presenting with features of classic or incomplete KD ferritin levels of 1176 ng/mL. In comparison to children

with KD in pre-pandemic times the current phenotype appendicitis. Subsequently, half of these children
included older children with more severe disease, required intensive care admission for hemodynamic
significant cardiac involvement and macrophage acti- instability. Apart from peripheral or periorbital edema,
vation syndrome (MAS) [10]. Again, only two tested none of them had features to suggest classic KD and five
positive for SARS-CoV-2 PCR, but eight tested positive tested positive for SARS-CoV-2 [12].
for the antibody. In both the groups, inflammatory
In a larger case series of 58 children (median age 9
markers (C-reactive protein, procalcitonin, ferritin,
years) from UK [13], all presented with fever and combi-
triglycerides, and D-dimer) were significantly elevated.
nations of abdominal pain (53%), diarrhea (52%) or rash
An abnormal echocardiogram with myocardial dysfunc-
(52%). Three clinical patterns were identified in this
tion and coronary artery abnormalities were observed in
cohort- fever with raised inflammatory markers (39.6%)
60% children, and two also had coronary aneurysms [10].
without features of KD, TSS or organ failure; shock
More recently, a French study [11] described a new (50%) with evidence of left ventricular dysfunction
syndrome complex of acute heart failure and hyper- (62%); and those fulfilling criteria for KD. Coronary
inflammation in children. Initial presentation predomi- artery aneurysms were noted across all three groups (8/
nantly included fever (100%) and gastro-intestinal 58). Compared to other inflammatory disorders, those
symptoms (80%) such as abdominal pain, vomiting and with PIMS-TS were older and had lower hemoglobin
diarrhea. Although mucocutaneous changes suggestive of levels and lymphocyte counts, and higher white blood
KD were noted, none of them met the criteria for classic cell count, neutrophil count and CRP levels (Table I)
KD. Echocardiography was significant for left ventri- [13].
cular dysfunction with a low ejection fraction. Inflam-
It appears that these children may develop single or
matory markers (CRP, D-dimer) were raised in all.
multi-organ dysfunction with persistent fever and
Coronary artery dilatation was seen in 17%, but as
features of inflammation (neutrophilia, elevated CRP and
opposed to classic KD, none of them developed coronary
lymphopenia). This may progress on to shock. In patients
aneurysms. Complete recovery was seen in 71% of
who turn out to be SARS-CoV-2 PCR negative, other
children, suggesting that myocardial edema rather than
microbial causes need to be actively considered and
necrosis was likely responsible for heart failure. This is in
excluded [4]. In addition to KD and TSS, secondary
contrast to the adult population, where myocardial
hemophagocytic lymphohistiocytosis (HLH) in associa-
necrosis has been incriminated in the pathogenesis [11].
tion with common tropical infections should also be
The importance of suspecting PIMS-TS in febrile considered in similar clinical settings. Based on available
adolescent children with gastrointestinal symptoms data, we speculate that there could be three distinct
during this pandemic cannot be overemphasized. This phenotypes of hyperinflammation in children (Table II).
unusual presentation was also reinforced in a case series
PATHOGENESIS
of eight children from UK, initially suspected to have
appendicitis [12]. Although they had very high CRP Approximately two-thirds of patients with PIMS-TS are
levels, abdominal imaging demonstrated non-specific COVID-19 PCR negative, a proportion of these being
features (e.g. lymphadenopathy or ileitis) rather than serologically positive, suggesting an immune-mediated
Table I Comparison of PIMS-TS With Classic KD, KDSS and TSS [13]
Features PIMS-TS (n=58) KD (n=1132) KDSS (n=45) TSS (n=46)
Age at onset, y 9.0 (5.7-14) 2.7 (1.4-4.7) 3.8 (0.2-18) 7.38 (2.4-15.4)
CRP, mg/L 229 (156-338) 67 (40-150) 193 (83-237) 201 (122-317)
Hemoglobin, g/L 92 (83-103) 111 (105-119) 107 (98-115) 114 (98-130)
Lymphocytes, ×109/L 0.8 (0.5-1.5) 2.8 (1.5-4.4) 1.6 (1-2.5) 0.63 (0.41-1.13)
Ferritin, µg/L 610 (359-1280) 200 (143-243) 301 (228-337) –
NT-Pro-BNP, pg/mL 788 (174-10548) 41 (12-102) 396 (57-1520) –
Troponin, ng/L 45 (8-294) 10 (10-20) 10 (10-30) –
D-dimer, ng/mL 3578 (2085-8235) 1650 (970-2660) 2580 (1460-2990)
Data are median (IQR); PIMS-TS: pediatric inflammatory multisystem syndrome-temporally related to SARS-CoV-2, KD: Kawasaki disease, KDSS:
Kawasaki disease shock syndrome, TSS: Toxic shock syndrome, CRP: C-reactive protein.

Table II Possible Phenotypes of SARS-CoV-2-Related Hyperinflammation in Children [4,18, 24]

Classic Kawasaki disease Pediatric inflammatory multisystem Macrophage activation syndrome
syndrome – temporally associated
with SARS-CoV-2
Clinical features
• Younger children (<5 y)* • Older children and adolescents • Adolescents
• Fever (usually >5 d) with any 4/5: • Fever with: • Unremitting fever
• Non purulent conjunctivitis • Gastrointestinal symptoms • Pulmonary involvement
• Cervical lymphadenopathy >1.5 cm • Mucocutanoeus changes • Organomegaly(Hepatosplenomegaly)
• Erythematous rash • Confusion or headache
• Mucositis- strawberry tongue • Single or multisystem dysfunction.
• Extremity changes- swelling/peeling • Rapid deterioration with refractory
• High incidence of coronary artery shock.
aneurysms.
• Refractory to therapy
Laboratory markers
• CRP ≥3.0 mg/dL and/or ESR ≥40 mm/h • High CRP • Cytopenia (at least 2 cell lines affected)
• Elevated ALT • Lymphopenia • Hypertriglyceridemia
• Albumin ≤3.0 g/dL • Neutrophilia in most • Hypofibrinogenemia
• WBC >15,000 • Abnormal fibrinogen • High ferritin
• Anemia for age • High D-Dimers • High AST
• Platelets >450000 (>7 d of fever) • High ferritin • Haemophagocytosis on bone marrow
• Urine analysis- 10 WBCs per high • Raised LDH aspirate
power field • Hypoalbuminemia • Low or absent NK cell activity
• Transaminitis • Elevated soluble CD25 levels
• Elevated troponin, NT-proBNP
Echocardiogram
• Coronary artery dilatation or aneurysms. • Left ventricular dysfunction • Left ventricular dysfunction
• Myocarditis • Coronary artery dilatation or aneurysm
• Valvulitis
• Pericardial effusion
• Coronary artery dilatation
*We believe that children under 1 year of age are at particular risk of coronary aneurysms in KD seen in COVID era (unpublished data from authors).
CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; WBC: white blood cell; AST: aspartate aminotransferase; ALT: alanine
aminotransferase; LDH: Lactate dehydrogenase; BNP: B-type natriuretic peptide.
pathogenesis over a direct virus invasion-mediated tissue epitopes on S protein are not [15,16]. Weak antibody
injury. Infection with COVID-19 triggers the formation coated virus gets internalized by Fc receptors, followed
of antibodies to viral surface epitopes. Virus neutrali- by endosomal release of the virion and subsequent Toll-
zation is a direct function of the stochiometric concen- like receptor and cytosolic RNA sensor triggered IFN α
tration and affinity of the antibodies. It is believed that responses. These antibody dependent enhancement
low titer non-neutralizing antibodies may accentuate (ADE) responses have been implicated in COVID-19
virus triggered immune responses instead, thereby induced immune injury. Although evidence base for this
increasing the risk of severe illness in affected individuals pathway is demonstrated for coronaviruses [16], the
[14]. While blocking antibodies against the angiotensin exact role in PIMS-TS is only speculative [17].
converting enzyme (ACE) receptor binding regions (such
MANAGEMENT
as the RBD and HR2 region of S protein) are deemed
protective, those directed against nucleocapsid and other Conventionally, treatment of KD involves use of

intravenous immunoglobulin (IVIG) and high dose circumstances (in children with high CRP levels and
aspirin as first line agents [18]. The use of IVIG for those refractory to IVIG/corticosteroids) either in
PIMS-TS may help in facilitating neutralization of virus controlled clinical trials or by clinicians experienced in
and associated superantigens and downregulation of the use of biologics. Where considered appropriate, therapy
inflammatory cytokines [19,20]. IVIG (2 g/kg) has been with biologics such as tocilizumab (8 mg/kg) or
used in most published series on PIMS-TS as first line infliximab (5 mg/kg) should be considered. Based on
therapy. The effects; however, may be short-lived [9,10]. existing evidence, suggested management of children
In those with features of classic KD, it would be with SARS-CoV-2 related hyperinflammation has been
appropriate to consider use of aspirin (30-50 mg/kg/day summarized in figure 1.
followed by 3-5 mg/kg/day) along with IVIG [18]. The
Apart from immunomodulation, supportive care
role of aspirin in children with hyperinflammation
plays a key role in the management of these children.
without features of KD is not known, and we believe that
Deterioration can be rapid, and it is important for clinic-
it has a limited role in these children. Although the role of
ians to monitor for signs of worsening inflammation [4].
anticoagulation is not clearly defined, it should be
considered on a case-by-case basis in children with FUTURE DIRECTIONS
hyperinflammatory syndrome. The choice of anti-
The important answers lie in understanding the immune
coagulation and their dosing regimen would also depend
origins of this condition. There is a need for clinical trials
on the presence of coronary aneurysms.
using adaptive designs (Bayesian methodology) which
In select cases, especially those who do not respond to would enable us to evaluate therapies including IL-6,
IVIG, adjunctive immunomodulatory therapy may be IL-1 and anti-TNF blockade in children with this
necessary to control inflammation. It is known that use of syndrome.
corticosteroids in KD is associated with earlier resolution
of fever and lower incidence of coronary artery A. Supportive care
abnormalities [18,21]. Corticosteroids are also used as first • Empirical antibiotics after obtaining blood cultures for
suspected or evident bacterial infection.
line therapy in children with MAS. On this basis, it is • Intensive care support including vasopressors and
plausible that these agents may be effective in PIMS-TS, assisted ventilation where indicated.
especially in those with features of cytokine release B. Specific management
syndrome (CRS). Recently published case series have
shown that corticosteroids (initially pulse intravenous • Intravenous immunoglobulin (2g/kg)*
methylprednisolone 10 mg/kg/day for 3 days followed by • Consider aspirin (30-50mg/kg/d followed by 3-5mg/kg/d)
in those with classic Kawasaki disease.
oral prednisolone in a gradual tapering regimen) are useful
adjuncts to IVIG in patients with PIMS-TS [9,10,21]. Persistent inflammation
Whilst not much is known about the pathogenesis of (Fever with raised inflammatory markers)
PIMS-TS, it is clear that there is elevation of cytokines ↓
• Intravenous methylprednisolone (10mg/kg/day) for 3 d
such as IL-1, IL-6, IL-18 and IFN-α in most children who • Consider oral steroids (1-2mg/kg/d, weaning dose over
develop MAS [22]. Although this does not necessarily 2 wk) for those with mild but persistent symptoms or
establish causality, specific cytokine blockade has signs of inflammation.
resulted in remission of MAS on many occasions [23].
Also, specific blockade of TNF-α with infliximab has
Persistent inflammation
been tried in children with KD resistant to IVIG [18]. (Fever with very high inflammatory markers)
Along with IL-6, several other cytokine blockade #
↓
therapies are currently under evaluation in adults with Biologics
• Tocilizumab (8 mg/kg)
COVID-19. As we understand more about targeted
• Infliximab (5 mg/kg)
therapy in adults with COVID induced CRS, we might • Anakinra (1-2 mg/kg/d to a maximum of 8 mg/kg/d)
consider trials of these agents in PIMS-TS [24,25].
*Note: If IVIG is not available or is contraindicated, consider upfront use of
Extrapolating these data, it is possible that there may be a corticosteroids; where possible, obtain blood samples for SARS-CoV-2
role for specific cytokine blockade in PIMS-TS as well. antibody testing or future research prior to administration of IVIG; Choice of
anticoagulation and their dosing regimen would depend on presence of
Apart from one case report describing the use of coronary artery aneurysms.
#
tocilizumab in a child with KD and SARS-CoV-2 [6], Only in centers with experience in use of biologics or in controlled clinical
trials.
data on use of biologics for this indication are still
lacking. Until such data are available, it would be Fig. 1 Suggested management of SARS-COV-2 related hyper-
reasonable to consider these therapies only under special inflammation in children.

Despite the emerging literature, there are still a lot of system-inflammatory-syndrome-temporally-associated-

unknowns regarding SARS-CoV-2. It is important to covid-19. Accessed May 5, 2020.
gather data on the condition to understand the damage 5. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Bradley
caused and risk for recurrence as well as long term SJ, et al. COVID-19 and Kawasaki disease: novel virus and
novel case. Hosp Pediatr. 2020 Jun; 10(6): 537-540. [E-
implications including the risk for autoimmune disease
pub ahead of print].
later in life. Real time surveillance studies such as the 6. Balasubramanian S, Nagendran TM, Ramachandran B,
WHO clinical data platform (https://apps.who.int/iris/ Ramanan AV. Hyper-inflammatory syndrome in a child
handle/10665/332236) and the British Pediatric Surveil- with COVID-19 treated successfully with intravenous
lance Unit (BPSU) study (https://www.rcpch.ac.uk/work- immunoglobulin and tocilizumab. Indian Pediatr. 2020;
we-do/bpsu/study-multisystem-inflammatory- syndrome- S097475591600180. [E-pub ahead of print].
kawasaki-disease-toxic-shock-syndrome) can gather 7. Multisystem inflammatory syndrome in children and
information to help further our understanding of this adolescents with COVID-19. 15 May 2020 Scientific brief:
disease. There is now an overwhelming need for World Health Organisation. Available from: https://www.
who.int/publications-detail/multisystem-inflammatory-
registries for data collection and integration, especially in
syndrome-in-children-and-adolescents-with-covid-19.
India [26,27]. Going forward, multicenter and perhaps Accessed May 31, 2020.
multi-national collaborative studies may be required to 8. Centers for Disease Control and Prevention. Emergency
fill existing gaps in our knowledge of the current preparedness and response: Health alert network.
pandemic and the new syndrome in children. Published May 14, 2020. Available from: https://
emergency.cdc.gov/han/ 2020/han00432.asp. Accessed
In the Indian context, we perceive a definite need for May 22, 2020.
increased awareness of this unique clinical syndrome 9. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson
amongst parents and pediatricians alike in the midst of N, Theocharis P. Hyperinflammatory shock in children
multitude of several common infections such as dengue, during COVID-19 pandemic. Lancet. 2020 May 23; 395
when a child presents with fever with variable (10237):1607-1608.
accompanying symptoms and signs and raised 10. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M,
inflammatory markers. Ciuffeda M, et al. An outbreak of severe Kawasaki-like
disease at the Italian epicentre of the SARS-CoV-2
Contributors: CB, LG, AVR: substantial contribution to the epidemic: An observational cohort study. Lancet. 2020;
conception and design of the work, preparation and finalization 395: 1771-78.
of the draft; CB, LG, SB, SS, AVR: substantial contributions to 11. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A,
the acquisition, analysis, and interpretation of data for the work; Abakka S, et al. Acute heart failure in multisystem
SB, SS, AVR: Critical Revision for important intellectual inflammatory syndrome in children [MIS-C] in the context
content; CB, LG, SB, SS, AVR: final approval of the version to be of global SARS-CoV-2 pandemic. Circulation. 2020 May
published, and agreement to be accountable for all aspects of the 17; CIRCULATIONAHA.120.048360. [E-pub ahead for
work in ensuring that questions related to the accuracy or print].
integrity of any part of the work are appropriately investigated 12. Tullie L, Ford K, Bisharat M, Watson T, Thakkar H,
and resolved. Mullassery D, et al. Gastrointestinal features in children
Funding: None; Competing interests: None stated. with COVID-19: an observation of varied presentation in
eight children. Lancet Child Adolesc Health. 2020;4: e19-
REFERENCES
e20.
1. Balasubramanian S, Rao NM, Goenka A, Roderick M, 13. Whittaker E, Bamford A, Kenny J, et al. Clinical
Ramanan AV. Coronavirus disease [COVID-19] in characteristics of 58 children with a pediatric inflammatory
children - What we know so far and what we do not. Indian multisystem syndrome temporally associated with SARS-
Pediatr. 2020; 57(5):435-442. CoV-2. JAMA. 2020; e2010369. [E-pub ahead for print].
2. Meena J, Yadav J, Saini L, Yadav A, Kumar J. Clinical 14. Yu H, Sun B, Fang Z, Zhao J, Liu X, Li Y, et al. Distinct
features and outcome of SARS-CoV-2 infection in features of SARS-CoV-2-specific IgA response in
children: A systematic review and meta-analysis. Indian COVID-19 patients. European Resp J. 2020; 2001526. [E-
Pediatr. 2020;S097475591600203. [published online pub ahead for print].
ahead of print, 2020 Jun 24]. 15. Iwasaki A, Yang Y. The potential danger of suboptimal
3. European Centre for Disease Prevention and Control. antibody responses in COVID-19. Nature Reviews
Pediatric inflammatory multisystem syndrome and SARS- Immunology. 2020. Available from: http://www.nature.
CoV-2 infection in children – 15 May, 2020. ECDC: com/articles/s41577-020-0321-6. Accessed May 29, 2020.
Stockholm; 2020. 16. Wang Q, Zhang L, Kuwahara K, Li L, Liu Z, Li T, et al.
4. Royal College of Pediatrics and Child Health. Guidance– Immunodominant SARS coronavirus epitopes in humans
Pediatric multisystem inflammatory syndrome temporally elicited both enhancing and neutralizing effects on
associated with COVID-19, 2020. Available from: https:// infection in non-human primates. ACS Infect Dis. 2016;
www.rcpch.ac.uk/resources/guidance-pediatric-multi 2(5):361-376.

17. Shen L, Fanger MW. Secretory IgA antibodies synergize 22. Schulert GS, Grom AA. Pathogenesis of macrophage
with IgG in promoting ADCC by human polymor- activation syndrome and potential for cytokine- directed
phonuclear cells, monocytes, and lymphocytes. Cellular therapies. Annu Rev Med. 2015; 66:145-59.
Immunology. 1981; 59(1):75-81. 23. Schulert GS, Grom AA. Macrophage activation syndrome
18. McCrindle BW, Rowley AH, Newburger JW, Burns JC, and cytokine-directed therapies. Best Pract Res Clin
Bolger AF, Gewitz M, et al. Diagnosis, treatment, and Rheumatol. 2014; 28:277-92.
long-term management of Kawasaki disease: A scientific 24. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall
statement for health professionals from the American Heart RS, Manson JJ, et al. COVID 19: Consider cytokine storm
Association. Circulation. 2017;135: e927-e99. syndromes and immunosuppression. Lancet. 2020;
19. Burns JC, Franco A. The immunomodulatory effects of 395:1033-34.
intravenous immunoglobulin therapy in Kawasaki disease. 25. Pacha O, Sallman MA, Evans SE. COVID-19: A case for
Expert Rev Clin Immunol. 2015;11:819-25. inhibiting IL-17? Nat Rev Immunol. 2020; 20:345-46.
20. Lo MS, Newburger JW. Role of intravenous 26. Acharyya BC, Acharyya S, Das D. Novel coronavirus
immunoglobulin in the treatment of Kawasaki disease. Int J mimicking kawasaki disease in an infant. Indian Pediatr.
Rheum Dis. 2018;21:64-9. 2020; S097475591600184 [published online ahead of
21. Kobayashi T, Saji T, Otani T, Takeuchi K, Nakamura T, print, 2020 May 22].
Arakawa H, et al. Efficacy of immunoglobulin plus 27. Rauf A, Vijayan A, John ST, Hrishnan R, Latheef A.
prednisolone for prevention of coronary artery Multisystem inflammatory syndrome with features of
abnormalities in severe Kawasaki disease [RAISE study]: atypical Kawasaki disease during COVID-19 pandemic.
A randomised, open-label, blinded-endpoints trial. Lancet. Indian J Pediatr. 2020; S12098020033571 [published
2012; 379:1613-20. online ahead of print, 2020 May 28].
ADVERTISEMENT

SPECIAL ARTICLE
Cardiac Involvement in Children With COVID-19

UTKARSH KOHLI1AND RAKESH LODHA2
From 1Section of Pediatric Cardiology, Division of Pediatrics, Comer Children’s Hospital and Pritzker School of Medicine of the
University of Chicago, Chicago, IL, USA; and 2Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Correspondence to: Dr Utkarsh Kohli, Assistant Professor of Pediatrics, Section of Pediatric Cardiology, Division of Pediatrics,
University of Chicago, 5481 S Maryland Ave., RM-C104E, MC 4051, Chicago, IL 60637, USA. utkarshkohli@gmail.com
In contrast to adults, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually leads to a mild illness in children. However,
a few children have been reported to have severe manifestations including pneumonia, acute kidney injury, multi-organ failure and cardiac
injury. This review focuses on cardiac involvement during SARS-CoV-2 infection and the recently described likely immune mediated post-
COVID-19 syndrome. Therapeutic strategies for cardiac dysfunction in both these settings are briefly discussed.
Keywords: SARS-CoV-2, MIS-C, Myocarditis, Coronary dilation, Hypotension, Shock.
Published online: August 07, 2020; PII: S097475591600222
W
e are currently in the midst of a SARS- admission; use of inotropes was reported in 12 (25%)
CoV-2 mediated novel coronavirus patients admitted to a North American PICU in a
disease 2019 (COVID-19) pandemic. In recent study [4]. The plasma concentration of cardiac
contrast to adults, SARS-CoV-2 mostly bio-markers and echocardiographic findings in these
leads to a mild illness in children typically manifested as patients were not reported, therefore it is unclear if
fever, cough or gastrointestinal symptoms [1,2]. How- inotropic requirement was due to primary cardiac
ever, a few children have been reported to manifest severe dysfunction [4].
disease which has been characterized by pneumonia,
Cardiac involvement in patients with COVID-19 has
acute kidney injury, liver injury, metabolic acidosis,
included elevation in cardiac biomarkers such as
neurological injury, rhabdomyolysis, multi-organ system
troponin, CPK-MB, and pro-brain type natriuretic
failure, and cardiac injury [1,3-5]. This review focuses on
peptide (pro-BNP), echocardiographic abnormalities
cardiac involvement during COVID-19 infection and the
such as diminished left ventricular function with
multisystem inflammatory syndrome in children (MIS-C)
segmental or global wall motion abnormality and coro-
[6,7]. Therapeutic strategies for cardiac dysfunction in
nary artery dilation, and electrical abnormalities such as
both these settings are briefly discussed.
sinus tachycardia, atrial arrhythmias, non sustained
CARDIAC INVOLVEMENT IN SARS-COV-2 ventricular tachycardia, first-degree atrioventricular
INFECTION block, premature atrial and ventricular contractions, and
incomplete right bundle branch block [3,12-17] (Table
Cardiac involvement, which can manifest as acute
1). In one of the largest pediatric series (n=2135) from
myocardial injury with elevated plasma troponin
China, 0.6% of children had symptomatic myocardial
concentration, acute coronary events, heart failure and
injury and heart failure [18,19].
arrhythmias is both common and associated with a higher
morbidity and mortality in adults with COVID-19 [8-10]. It is difficult to draw any firm conclusions, given the
Hypothesized mechanisms of cardiac injury include small numbers and lack of any systematic prospective
direct viral invasion leading to cardiomyocyte death and studies. However, currently available data indicates that
inflammation and indirect mechanisms of injury - cardiac cardiac involvement in children with COVID-19 is not
stress due to respiratory failure and hypoxemia and common. In addition to clinical evaluation, electro-
cardiac inflammation secondary to severe systemic cardiography and cardiac imaging, cardiac biomarkers
hyper-inflammation, which is thought to be mediated by such as plasma troponin, CK-MB and pro-BNP may be
cytokines such as interleukin (IL)-6, IL-2, IL-7, TNF helpful in diagnosis. IVIG may have a role in treatment of
(tumor necrosis factor)-α and IFN (interferon)-γ [11]. children with cardiac involvement. The role of other
Cardiac involvement during COVID-19 is not common in drugs such as remdesivir and hydroxychloroquine is
children who require pediatric intensive care unit (PICU) unclear at this time.

KOHLI & LODHA CARDIAC INVOLVEMENT AND COVID-19
Table 1 Cardiac Involvement in Children With Coronavirus Disease 19

Author, No. of Age, sex, Clinical Cardiac biomarkers Echo findings Treatment
patients ethnicity presentation and ECG findings
Cui, et al. [3], 55 d, F Respiratory symptoms Mild ↑ troponin - -
1 Chinese
Giacomet, et al. 2 mo Fever and sinus ↑ troponin and Hypokinesia of the IVIG (2 g/kg)
[12],1 tachycardia ↑ BNP inferior LV wall and
the inferior interventri-
cular septum.
Mild ↑ LVEF
Sun, et al. [13], 13 mo, M Multiorgan dysfunc- - - Antiviral drugs,
1 Chinese tion including cardiac Glucocorticoids,
dysfunction IVIG, and
Plasmapheresis
Xia, et al. [14], 1 d-14 y Fever, cough, ↑CPK-MB (n=5), - -
5 Chinese GI symptoms sinus tachycardia
(n=1), atrial tachy
cardia (n=1), PACs,
PVCs and prolonged
PR interval (n=1),
and incomplete RBBB
(n=1)
Su, et al. [15], 11 mo - Fever, cough ↑CPK-MB - Lopinavir/
6 9.75 y, Ritonavir,
3M/3F Interferon
Chinese
Samuel, et al. 12-20 y ↑troponin (n=2), LV dysfunction (n=2), Beta-blocker (n=2),
[16], 6 monomorphic VT LV dilation (n=1), Amiodarone (n=1)
(n=5), sustained atrial large circumferential
tachycardia (n=1) pericardial effusion
(n=1)
Oberweis, et al. 8 y, M Fever, cough, malaise, ↑ troponin, LV dysfunction, trace IVIG (2g/kg)
[17], 1 African weight loss ↑ BNP mitral regurgitation
and small pericardial
effusion
LV: Left ventricle; BNP: Brain type natriuretic peptide; IVIG: Intravenous Immune Globulin; PAC: Premature Atrial Contraction; PVC: Premature
Ventricular Contraction; CPK-MB: Creatine Phosphokinase-Muscle Brain subtype; LVEF: Left Ventricular Ejection Fraction.
CARDIAC INVOLVEMENT IN MIS-C cardiac chamber size and/or function, coronary artery
abnormalities (ectasia, aneurysm) or elevated cardiac
A few weeks following the peak of COVID-19 epidemic
biomarkers such as troponin or pro-BNP is not only
in the US and the European Union, a novel systemic
common in children with MIS-C but can also be severe
illness which clinically overlaps with Kawasaki disease
(Web Table I). A vast majority of children with MIS-C
with or without shock syndrome, macrophage activation
had been previously healthy; a few have had minor
syndrome (MAS) and toxic shock syndrome (TSS) was
comorbidities such as asthma and obesity. In addition to
reported in children. This entity was labeled as
fever and weakness/malaise, gastrointestinal symptoms
Multisystem inflammatory syndrome in children (MIS-
have been common at presentation. Many of these
C) by the Centers for Disease Control and Prevention
children have had marked hemodynamic instability
(CDC), USA and by the World Health Organization
requiring inotropic support and intensive care at
(WHO) [6,7]. A few cases have also been reported from
admission. In addition, a small proportion has required
India [20].
extracorporeal membrane oxygenation support; though,
Cardiac involvement as evidenced by perturbation of mortality has been low [20-27]. In contrast to patients

with typical Kawasaki disease, atypical features modifying therapies such as anakinra, tocilizumab and
including a higher incidence of cardiac involvement convalescent plasma have been used in patients with both
(60%), shock syndrome like features (50%), MAS (50%) acute COVID-19 and MIS-C, their role has not been
and need for steroids following IVIG administration systematically evaluated. Given the potential risk of
(80%) were noted in a previous study [22]. thrombotic complications, we also initiate aspirin and
low molecular weight heparin at admission, both of which
The precise mechanisms that underlie genesis of
we discontinue upon normalization of inflammatory
MIS-C and its cardiac manifestations are yet unknown.
markers. In addition to aspirin and low molecular weight
However, given the fact that a vast majority of children
heparin, we have typically discharged these patients on
have presented 4-6 weeks after the peak of the local
oral steroids which are gradually tapered as guided by
COVID-19 epidemic, many have been SARS-CoV-2
their clinical status and cardiac and inflammatory
PCR negative but antibody positive, have had markedly
biomarkers. Cardiac imaging with a focus on coronary
elevated inflammatory markers such as C-reactive
arteries is obtained at regular intervals after discharge
protein, erythrocyte sedimentation rate, fibrinogen,
[28].
procalcitonin, ferritin, or interleukin 6, and have
responded well to IVIG and immunomodulators; an Cardiac involvement in children with COVID-19 is
immune origin is likely. Genetic factors may underlie the uncommon; however, a handful of patients have had
overall rarity of MIS-C and relative preponderance in severe involvement with markedly diminished
African Americans. ventricular function and hemodynamic instability. These
patients have benefited from IVIG. The role of antivirals
Given the multiorgan dysfunction and potential for
such as remdesivir, hydroxychloroquine, and adjunctive
sudden and severe decompensation in patients with MIS-
immunomodulatory therapies in patients with COVID-19
C, our practice has been to admit these patients to PICU
and cardiac involvement is unclear at this time. Cardiac
where they are cared for by a team which involves
involvement as evidenced by perturbation of cardiac
specialists from pediatric rheumatology/immunology,
chamber size and/or function, coronary artery abnor-
pediatric critical care, pediatric cardiology, pediatric
malities (ectasia, aneurysm) or elevated cardiac bio-
infectious diseases, and pediatric hematology. Inotropes
markers such as troponin or pro-BNP is not only common
should be initiated in children with MIS-C if clinically
in children with MIS-C but can also be severe. These
indicated and ECMO should be reserved for children
children have responded to IVIG and or corticosteroids.
with inotrope-refractory shock. In addition to clinical
A few have required additional immunomodulators such
markers, mixed venous oxygen saturation and plasma
as anakinra and tocilizumab.
lactate can be used to guide therapy. A vast majority of
children with MIS-C have responded well to IVIG (1-2 g/ REFERENCES
kg), which as per the recently proposed American 1. Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R,
College of Rheumatology guidelines [28] should be the Perlini S, et al. Severe acute respiratory syndrome
initial therapeutic agent. Though the data are scarce, coronavirus 2 (SARS-CoV-2) infection in children and
patients with suboptimal clinical response (hemodynamic adolescents: A Systematic Review [published online ahead
instability) or biochemical response (persistent elevation of print, 2020 Apr 22]. JAMA Pediatr. 2020;10.1001/
in inflammatory markers) to IVIG have benefitted from jamapediatrics.2020.1467.
steroids (intravenous methylprednisolone 2 mg/kg/day) 2. Ludvigsson JF. Systematic review of COVID-19 in
children shows milder cases and a better prognosis than
or immunomodulators such as anakinra (interleukin-1
adults. Acta Paediatr. 2020;109:1088-95.
antagonist) (2-8 mg/kg/day subcutaneous injection once 3. Cui Y, Tian M, Huang D, Wang X, Huang Y, Fan Li, et al.
or twice a day, maximum dose: 100 mg twice a day) and A 55-day-old female infant infected with 2019 novel
tocilizumab (interleukin-6 antagonist). The dosing of coronavirus disease: Presenting with pneumonia, liver
tocilizumab for systemic onset juvenile idiopathic injury, and heart damage. J Infect Dis. 2020;221:1775-81.
arthritis is 12 mg/kg intravenous or 162 mg subcutaneous 4. Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ,
every other week for those weighing less than 30 kg and 8 Ross CE, McKiernan CA, et al. Characteristics and
mg/kg intravenous every other week or 162 mg outcomes of children with coronavirus disease 2019
subcutaneous every week for those weighing >30 kg. The (COVID-19) infection admitted to US and Canadian
pediatric intensive care units [published online ahead of
optimal dose and dosing frequency for MIS-C is not
print, 2020 May 11]. JAMA Pediatr. 2020;10.1001/
known; intravenous doses of 400-800 mg and a jamapediatrics.2020.1948.
subcutaneous dose of 162 mg has been used in adults with 5. Gefen AM, Palumbo N, Nathan SK, Singer PS,
COVID-19 associated cytokine release syndrome [29], Castellanos-Reyes LJ, Sethna CB. Pediatric COVID-19-
and 8 mg/kg in children [30]. Though adjunctive immune associated rhabdomyolysis: A case report. Pediatr Nephrol.

2020;35:1517-20. Marcialis MA. Children’s heart and COVID-19: Up-to-

6. Centers for Disease Control and Prevention. Multisystem date evidence in the form of a systematic review. Eur J
Inflammatory Syndrome in Children (MIS-C) Associated Pediatr. 2020;179:1079-87.
with Coronavirus Disease 2019 (COVID-19). Available 20. Dhanalakshmi K, Venkataraman A, Balasubramanian S,
from: https://emergency.cdc.gov/han/2020/han00432.asp. Madhusudan M, Amperayani S, Putilibai S, et al.
Accessed May 29, 2020 Epidemiological and clinical profile of pediatric
7. World Health Organization. Multisystem inflammatory inflammatory multisystem syndrome - temporally
syndrome in children and adolescents temporally related to associated with SARS-CoV-2 (PIMS-TS) in Indian
COVID-19 Available from: https://www.who.int/news- children [published online ahead of print, 2020 Aug
room/commentaries/detail/multisystem-inflammatory- 6]. Indian Pediatr. 2020; S097475591600220.
syndrome-in-children-and-adolescents-with-covid-19. 21. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A,
Accessed May 29, 2020 Abakka S, et al. Acute heart failure in multisystem
8. Bansal M. Cardiovascular disease and COVID-19. inflammatory syndrome in children (MIS-C) in the context
Diabetes Metab Syndr. 2020;14:247-50. of global SARS-CoV-2 pandemic [published online ahead
9. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, of print, 2020 May 17]. Circulation. 2020;10.1161/
Tomasoni D, et al. Cardiac involvement in a patient with CIRCULATIONAHA.120.048360.
coronavirus disease 2019 (COVID-19). JAMA Cardiol. 22. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M,
2020;5:1-6. Ciuffreda M, et al. An outbreak of severe Kawasaki-like
10. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. disease at the Italian epicentre of the SARS-CoV-2
Association of cardiac injury with mortality in hospitalized epidemic: An observational cohort study. Lancet.
patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;395:1771-78.
2020;5:802-10. 23. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson
11. Akhmerov A, Marbán E. COVID-19 and the heart. Circ N, Theocharis P. Hyper inflammatory shock in children
Res. 2020;126:1443 55. during COVID-19 pandemic. Lancet. 2020;395:1607-8.
12. Giacomet V, Manfredini VA, Meraviglia G, Peri CF, Sala 24. Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J,
A, Longoni E, et al. Acute inflammation and elevated Diorio C, et al. Multisystem inflammatory syndrome in
cardiac markers in a two-month-old infant with severe children during the COVID-19 pandemic: A case series. J
acute respiratory syndrome coronavirus 2 infection Pediatric Infect Dis Soc. 2020;9:393-8.
presenting with cardiac symptoms. Pediatr Infect Dis J. 25. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams
2020;39:e149-51. MM, Son MBF, et al. Multisystem inflammatory syndrome
13. Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang F, et al. Clinical in U.S. children and adolescents. N Engl J Med.
features of severe pediatric patients with coronavirus 2020;383:334-46.
disease 2019 in Wuhan: A single centers observational 26. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse
study. World J Pediatr. 2020;16:251-9. A, Rawlands J, et al. Multisystem inflammatory syndrome
14. Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT in children in New York State. N Engl J Med.
features in pediatric patients with COVID-19 infection: 2020;383:347-58.
Different points from adults. Pediatr Pulmonol. 2020; 27. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE,
55:1169 74. Shah P, et al. Clinical Characteristics of 58 Children With a
15. Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The Pediatric Inflammatory Multisystem Syndrome
different clinical characteristics of corona virus disease Temporally Associated With SARS-CoV-2 [published
cases between children and their families in China - the online ahead of print, 2020 Jun 8]. JAMA. 2020;e2010369.
character of children with COVID-19. Emerg Microbes 28. American College of Rheumatology. Clinical Guidance for
Infect. 2020;9:707-13. Pediatric Patients with Multisystem Inflammatory
16. Samuel S, Friedman RA, Sharma C, Ganigara M, Mitchell Syndrome in Children (MIS-C) Associated with SARS-
E, Schleien C, et al. Incidence of arrhythmias and electro- CoV-2 and Hyperinflammation in COVID-19. Available
cardiographic abnormalities in symptomatic pediatric from: https://www.rheumatology.org/ Portals/0/Files/
patients with PCR positive SARS-CoV-2 infection ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-
including drug induced changes in the corrected QT interval Hyperinflammation .pdf. Accessed August 7, 2020.
(QTc). Heart Rhythm. 2020;S1547-5271: 30632-9. 29. Hassoun A, Thottacherry ED, Muklewicz J, Aziz QU,
17. Oberweis ML, Codreanu A, Boehm W, Olivier D, Pierron Edwards J. Utilizing tocilizumab for the treatment of
C, Tsobo C, et al. Pediatric Life-threatening coronavirus cytokine release syndrome in COVID-19. J Clin Virol.
disease 2019 with myocarditis. Pediatr Infect Dis J. 2020;128:104443.
2020;39:e147-e149. 30. Balasubramanian S, Nagendran TM, Ramachandran B,
18. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Ramanan AV. Hyper-inflammatory syndrome in a child
Epidemiology of COVID-19 among children in China. with COVID-19 treated successfully with intravenous
Pediatrics. 2020;e20200702. immunoglobulin and tocilizumab. Indian Pediatr.
19. Sanna G, Serrau G, Bassareo PP, Neroni P, Fanos V, 2020;57:681-3.

Web Table I Cardiac Involvement in Children With MIS-C
Study Belhadjer, et al. Verdoni, et al. Riphagen, et al. Chiotos, et al. Feldstei, et al. Durfort, et al. Whittaker, et al.
[20] [21] [22] [23] [24] [25] [26]
Patients 35 10 8 6 186 99 58
KOHLI & LODHA
Age*, y 2-16 (median 10) 2.9-16 (mean 7.5) 4-13 (mean 8.9) 5-14 (mean 8.5) 3.3-12.5 0-5 (31%), 5.7-14
INDIAN PEDIATRICS
(median 8.3) 6-12 (42%) (median 9)
Male 51% 70% 62% 17% 62% 54% 66%
Chest pain 6 (17) NA 0 0 - 11 (11) -
Gastrointestinal Nausea, diarrhea Diarrhea 6 Diarrhea 7 (88) Diarrhea 4 (67) 171 (92) 79 (80) Abdominal Abdominal pain
symptoms (83) (60) Abdominal pain Abdominal pain/ pain 60 (61), nausea 31 (53), diarrhea
6 (75) Vomiting 5 (83) or vomiting 57 (58), 30 (52), vomiting
Vomiting 4 (50) diarrhea 49 (49) 26 (45)
Cardiogenic shock 28 (80) 5 (50) 8 (100) 6 (100) - 32 (32) 29 (50)
Arrhythmias 1 (3) 0 1 (12.5) 1 (17) 22 (12) - 4 (7)
Cardiac high- 347 (186-1267) Troponin I 1004 Troponin > 50 ng/L Troponin>0.3ng/mL Elevated troponin Elevated troponin 45 (8-294) ng/L
sensitivity troponin ng/mL [median (1862) ng/L, mean 4 (50%), mean (SD), 2/6 (33%), mean (SD), 64 (50) % 63 (71) (n=56)
concentration (range)] (SD) Elevated in 252.5 (103.9) ng/L 0.48 (0.22) ng/mL
5/9 (55)
BNP or NT-pro *NT-proBNP (n=5) 1255 (929) ng/L; Elevated 5/8 (62.5) BNP (> 100 pg/mL) Elevated BNP Elevated BNP *NT-proBNP 788
BNP 41484 (35811-52475) Elevated in 10 (100) 19961.4 (5567.6) 5 (100), 4671.4 (> 400 pg/mL) 74 (90) (174 -10548)
pg/mL; *BNP (n=28) ng/L (3,138.9) pg/mL 112 (73) pg/mL (n=29)
5743 (2648-11909)
pg/mL, median (range)
Systolic 35 (100) LVEF 5 (50) LVEF 6 (75) 4 (67) LVEF 71 (38); LVEF 51 (52), 32 (32) 18/29 (62)
ventricular <30% (28); LVEF 25-48% <30% <30%, 9 (5), LVEF pericardial effusion
dysfunction 30-50% (72) 30-55% 61 (33)
Coronary artery 6 (17) 2 (20) 1 (12.5) 1 (12.5) 15 (8)# 9 (9) 8 (14.5)
dilation (>2Z)
ECMO 10 (28) None 1 (12.5) 0 7 (4) 4 (4) 3 (5)
Inotropic support 28 (80) 2 (20) 8 (100) 5 (83) 89 (48) 61 (62) 27 (47)
IVIG 25 (71) 10 (80) 8 (100) 6 (100) 144 (77) 69 (70) 41 (71)
Corticosteroids 12 (34) 8 (80) 5 (62.5) 5 (83) 91 (49) 63 (64) 37 (64)
IL-1 receptor 3 (8) 0 0 1 (17) 24 (13) - 3 (5)
antagonist
Mortality 0 0 1 (12.5) 0 4 (2) 2 (2) 1 (2)
All values in no. (%) except *range (mean/median)or detailed; BNP: Brain type natriuretic peptide; NT-proBNP: N-terminal pro-brain type natriuretic peptide; LVEF: Left ventricular ejection fraction;
ECMO: Extracorporeal membrane oxygenation; IVIG: Intravenous immunoglobulin; corticosteroids: Intravenous corticosteroids; # z score>2.5.
VOLUME 57__OCTOBER 15, 2020

CARDIAC INVOLVEMENT AND COVID-19
REVIEW ARTICLE
Medical Expulsive Therapy for Urinary Stone Disease in Children

SELASIE Q GOKA AND LAWRENCE COPELOVITCH
From Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA, United States
Correspondence to: Dr Lawrence Copelovitch, The Children’s Hospital of Philadelphia, Division of Nephrology, 3501 Civic Center
Boulevard, Philadelphia, PA 19104, Copelovitch@email.chop.edu
The rising incidence of urinary stone disease in children requires pediatric practitioners to keep abreast of management
recommendations which are generally geared towards adults. Medical expulsive therapy (MET) is a non-surgical therapeutic option that
can be trialed in patients who present with uncomplicated symptomatic ureteral stones. Seminal articles published and indexed in
Medline on the topic of MET were extracted and reviewed. Studies suggest a potential benefit of alpha-blockade for the expulsion of
distal ureteral stones that are >5 mm but ≤10 mm in adults and possibly >4 mm in children. Conversely, there does not seem to be any
added benefit for MET in smaller stones (<5 mm) in which the spontaneous passage rate is high. Conclusions: The off-label use of
these medications is one of the several barriers which contribute to the underutilization of MET in children. However, these may be a
reasonable option in particular for older children and adolescents with the appropriate-sized stones.
Keywords: Alpha-blockers, Calculi, Nephrolithiasis, Tamsulosin.
U
rinary stone disease is a worldwide health and can also be mediated via the autonomic nervous
problem with increasing incidence and system [4].There are multiple different receptors types
prevalence in developed countries across and second messengers located throughout the ureter
Europe and Asia [1,2]. Clinical research in which seem to play important roles in mediating this
urinary stone disease has primarily focused on coordinated activity, the most relevant of which are a1-
interventions aimed at reducing the morbidity and costs adrenergic receptors, prostaglandin receptors and
associated with initial presentation and symptomatic phosphodiesterases [4]. Activation of any of the above
crises as well as long-term preventative strategies. Acute named receptor sites or increased phosphodiesterase
management strategies during a symptomatic event are activity typically leads to increased peristalsis [4]. The
often dictated by the degree of discomfort, associated theoretical principle behind MET is to administer a
infection, or the presence of an acute obstruction with medication which counteracts the contractile action of
resultant acute kidney injury. Additionally, the location the ureters, resulting in smooth muscle relaxation and
and size of the stone and any associated anatomical promoting the passage of stones from the ureter.
abnormality of the urinary tract might impact clinical Medications that have been studied in relation to ureteral
decision-making [3]. Interventions may involve the stones include a-blockers (e.g., tamsulosin), calcium
administering medications aimed at facilitating stone channel blockers (nifedipine) and phosphodiesterase
passage or surgical procedures which directly assist in inhibitors (tadalafil) [5]; although, the latter two
stone removal. The strategy of administering medications medications have not been studied in children [6,7].
to facilitate the passage of ureteric stones and ameliorate
renal colic is generally referred to as medical expulsive In order to adequately assess the effectiveness of
therapy (MET). The purpose of this review is to both MET, one must first consider the natural history and
summarize and critically appraise the MET literature with likelihood of spontaneous passage of a stone without
particular emphasis on children. medical intervention. In general, stones that are smaller in
size have been found to be more likely to pass
BACKGROUND
spontaneously. One study in adults demonstrated that
The ureter contains a layer of smooth muscle which the rate of spontaneous expulsion was 87% for ureteral
undergoes peristalsis and results in the propulsion of stones 1 mm in diameter, 76% for stones 2-4 mm, 60%
ureteral contents towards the bladder [4]. This can occur for stones 5-7 mm, 48% for stones 7-9 mm and 25%
both autonomously via the release of neurotransmitters for those larger than 9 mm [8]. In the pediatric population,

GOKA & COPELOVITCH URINARY STONE DISEASE IN CHILDREN
a retrospective study of 33 children revealed that 55% of the stones sooner than those on placebo (148.3 vs 248.7
children with calculi ≤3 mm passed their stones with hours) [16]. Subgroup analysis demonstrated that there
hydration and narcotic therapy alone. All children with was no benefit for tamsulosin therapy for subjects with
stones >4 mm required further intervention [9]. In stones ≤5 mm and that the entire beneficial effect was
addition, adult studies have demonstrated that the driven by those subjects with stones >5 mm. These
location of a stone within the ureter appears to affect the results perhaps explain the discrepant findings noted
likelihood of spontaneously passage. Distal and uretero- between the previous randomized controlled studies in
vesicular junction had the highest rate of spontaneous which the majority of stones were small and
expulsion at 75% and 79%, respectively, followed by mid underpowered to evaluate size effect.
ureteral and proximal ureter stones with rates of 60% and
In 2016, an updated meta-analysis of 55 randomized
48% [8]. Other less well defined factors that may play a
controlled trials (including 5990 patients) that evaluated
role include number of stones, and the degree of edema in
the effect of alpha blockers on ureteral stone expulsion
the ureters [10].
was performed by Hollingsworth, et al. [17]. The pooled
A meta-analysis of nine randomized controlled trials risk ratio (RR) for stone expulsion was 1.49 (95% CI 1.39 to
(1981-2005) reported on 693 adults using a-blockers or 1.61) for patients treated with alpha blockers as compared
calcium channel blockers as the primary therapy for MET to those who were treated with placebo [17]. The effect of
and stone passage as the primary outcome [11]. The MET in relation to the location of the stone revealed that
authors determined that subjects who received either Tamsulosin increased the rate of stone passage in the
tamsulosin or nifedipine had a 1.65 higher chance (95% upper and middle ureter (pooled RR of 1.48 with 95% CI
CI, 1·45-1·88) of passing their stones. Based on this study 1.05 to 2.10) and confirmed the benefit in distal ureteral
and similar meta-analyses [12], both the European stones (pooled RR of 1.49 with 95% CI 1.38 to 1.63) as
Association of Urology (EAU) and American Urologic compared to controls [17].
Association (AUA) included recommendations that
In summary it appears that MET, and in particular
allowed for patients with stones <6 mm or stones <10 mm,
alpha blockade, has beneficial effects on aiding expulsion
respectively, the option of a trial of MET [6,7].
of ureteral stones >5 mm in size in adults. This benefit
Adult studies: The Spontaneous Urinary Stone Passage appears to be most consistent for stones found in the
Enabled by Drugs (SUSPEND) trial consisted of 1167 distal ureter but may be beneficial for the management of
adults with a ureteral stone <10 mm. Subjects were stones >5 mm and <10 mm regardless of location.
randomized to receive either nifedipine 30 mg, tamsulosin
Pediatric studies: There are multiple factors which
0.4 mg or placebo [13]. There was no difference between
contribute to the limited use of MET in pediatric patients.
active treatment with MET and placebo or between
These include a lack of familiarity with MET by pediatric
tamsulosin and nifedipine. Further, no benefit was seen in
practitioners, a relatively larger stone size to the ureteral
patients with respect to stone size or location in the ureter
dimension ratio as compared to adults, physician and
[13]. Similar to the SUSPEND trial, Furyk, et al. [14] also
parental discomfort with off-label use of medications in
reported no difference in overall rates of stone passage
children, and a fear of potential poor tolerance of alpha-
between patients in tamsulosin or placebo groups.
blockers [18]. To highlight this point Ellison, et al. [19]
Importantly, in the subgroup with stones >5 mm there was
performed a retrospective study using the Market Scan
a 22.4% (95% CI 3.1 to 41.6, P=0.03) higher rate of stone
Commercial Claims and Encounters database to assess
passage in those who received tamsulosin as compared
how often MET was being offered to pediatric patients
to the placebo group [14]. The Tamsulosin for Urolithiasis
[19]. Overall 1325 children between the ages of 1-18 years
in the Emergency Department (STONE) study [15] did not
with either a renal or ureteral calculus were identified by
find a significantly better stone passage rate in patients
ICD 9 code. Of these only 13.2% received MET [19].
who received MET, as compared to placebo. In the largest
Nonetheless, several studies have examined the efficacy
randomized, double blind placebo controlled study to
of MET in the management of distal ureteral stones in the
date, Ye, et al. [16] examined the difference in distal
pediatric population with mixed results.
ureteral stone expulsion rates in 3296 patients receive
either 0.4 mg tamsulosin or placebo for 28 days [16]. A prospective, randomized trial of 39 children with
Results from the study demonstrated a statistically ureteral stones <10 mm in size compared the efficacy of
significant benefit for those patients who received ibuprofen alone as compared to doxazosin (0.03 mg/kg
tamsulosin (86% stone passage) versus those receiving daily) on stone passage rates [20]. During a mean follow
placebo (79% stone passage) with a P-value <0.001 [16]. up period of 19 days, there was no significant difference
Patients treated with tamsulosin were also found to pass between the groups in terms of expulsion rates and mean

time to expulsion [20]. Conversely, Erturhan, et al. prospective trials [10,20-22] and one cohort study [23].
demonstrated a benefit of doxazosin as compared to This analysis also demonstrated a higher stone expulsion
analgesia alone in a study of 45 children with distal rate (OR 2.71, 95% CI 1.49-4.91) associated with MET
ureteral calculi at three weeks follow-up [21]. In this study, usage but did not demonstrate shorter times to stone
only 28.6% patients in the control group had passage as compared to controls [26].
spontaneous expulsion of their stones as compared to
CONCLUSION
70.8% in the intervention group (P=0.005) [21]. It is
noteworthy; however, that the spontaneous expulsion Pediatric urinary stone disease is an evolving condition
rate in the control group was substantially lower than whose incidence and prevalence have increased over the
what has been reported in other similar pediatric studies last several decades [27]. In response to this increased
[10,20,22], thus potentially magnifying the effect of the burden, MET has been well studied and guidelines for its
MET. use in adults are already available [7,28]. The most
frequently studied medication has been tamsulosin,
Several studies have also examined the effect of
which potentially contributes to stone passage through
tamsulosin in children. A placebo-controlled prospective
the relaxation of ureteral smooth muscle thereby
trial in which 61 children with distal ureteral stones <12
promoting the promoting the passage of stones. Notably,
mm were randomized to receive either analgesia plus
stones <4-5 mm have a high likelihood of spontaneous
tamsulosin or analgesia with placebo, found that after
passage resulting in seemingly little added benefit of
four weeks, patients who received tamsulosin were
MET. Conversely, adult studies seem to suggest that
significantly more likely to have spontaneous stone
MET likely may increases the likelihood of stone passage
passage (87.8%) as compared to the placebo group
in patients with distal ureteral stones >5 mm and <10 mm
(64.2%) [10]. Additionally there was a significant
in size. Although, studies in children are few in number
difference in time to passage of the stone with those in the
and contain a limit number of patients, most studies
tamsulosin group passing stones on average 6 days
indicate that tamsulosin might be of benefit in children
earlier than the control group [10]. Aldaqadossi, et al. [22]
with ureteral stones ≥ 4 mm but less than 10-12mm [9].
demonstrated similar findings in 67 pediatric patients with
distal ureteral stones <10 mm; 87% of 33 children REFERENCES
receiving tamsulosin passed their stones with a mean time
1. Romero V, Akpinar H, Assimos DG. Kidney Stones: A
of 7.7 days while only 63% of the 34 controls passed their Global Picture of Prevalence, Incidence, and Associated
stones with a mean time of 18 days [22]. A multi-center Risk Factors. Rev Urol. 2010;12:e86-e96.
retrospective study compared 99 children prescribed 2. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic
tamsulosin for ureteral stones <10 mm to 99 propensity Diseases in America Project. Prevalence of kidney stones in
matched controls who were treated with analgesia alone the United States. Eur Urol. 2012;62:160-65.
[23]. At six week follow up, 55% of patients receiving MET 3. Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck
achieved stone expulsion as compared to 44% of controls AC, Gallucci M, et al. 2007 Guideline for the Management
(P=0.03) [23]. Logistic regression analysis adjusting for of Ureteral Calculi. Eur Urol. 2007;52:1610-31.
4. Canda AE, Turna B, Cinar GM, Nazlý O. Physiology and
stone size and location showed an odds ratio of 3.31 (95%
Pharmacology of the Human Ureter: Basis for Current and
CI 1.49-7.34) for spontaneous stone passage in children Future Treatments. Urol Int. 2007;78:289-98.
receiving tamsulosin as compared to those receiving 5. Kroczak T, Pace KT, Lee JY. Medical Expulsive Therapy:
analgesia alone [23]. Worthwhile or wishful thinking. Curr Urol Rep.
2017;18:29.
To date two pediatric meta-analyses have been
6. Segura JW, Preminger GM, Assimos DG, Dretler SP, Kahn
performed. A meta-analysis [24] including four of the RI, Lingeman JE, et al. Ureteral Stones Clinical Guidelines
previously cited studies [10,20,21,23] and one abstract Panel summary report on the management of ureteral
[25] included 465 subjects <18 years of age with ureteral calculi. The American Urological Association. J Urol.
stones demonstrated that MET significantly increased 1997;158:1915-21.
the odds of spontaneous stone passage (OR 2.21, 95% CI 7. Türk C, Knoll T, Seitz C, Skolarikos A, Chapple C,
1.40 -3.49) as compared to controls. Furthermore, when McClinton S. Medical expulsive therapy for
the analysis was restricted to the randomized controlled ureterolithiasis: The EAU Recommendations in 2016. Eur
trials [10,20,21], MET significantly increased the odds of Urol. 2017;71:504-7.
8. Coll DM, Varanelli MJ, Smith RC. Relationship of
spontaneous stone passage (OR 4.06, 95% CI 1.84-8.95)
spontaneous passage of ureteral calculi to stone size and
as compared to controls [24]. The second meta-analysis location as revealed by unenhanced helical CT. Am J
[26] included 406 children who were treated exclusively Roentgenol. 2002;178:101-3.
with a-blockers from four of the previously cited 9. Van Savage JG, Palanca LG, Andersen RD, Rao GS,

Slaughenhoupt BL. Treatment of distal ureteral stones in 2017;13:510.

children: Similarities to the American Urological 19. Ellison JS, Merguerian PA, Fu BC, Holt SK, Lendvay TS,
Association guidelines in adults. J Urol. 2000;164:1089-93. Gore JL, et al. Use of medical expulsive therapy in children:
10. Mokhless I, Zahran AR, Youssif M, Fahmy A. Tamsulosin An assessment of nationwide practice patterns and
for the management of distal ureteral stones in children: A outcomes. J Pediatr Urol. 2017;13:509.e1-509.e7.
prospective randomized study. J Pediatr Urol. 2012;8:544-8 20. Aydogdu O, Burgu B, Gucuk A, Suer E, Soygur T.
11. Hollingsworth JM, Rogers MA, Kaufman SR, Bradford TJ, Effectiveness of Doxazosin in treatment of distal ureteral
Saint S, Wei JT, et al. Medical therapy to facilitate urinary stones in children. J Urol. 2009;182:2880-4.
stone passage: a meta-analysis. Lancet. 2006;368:1171-9. 21. Erturhan S, Bayrak O, Sarica K, Seckiner I, Baturu M, Sen
12. Seitz C, Liatsikos E, Porpiglia F, Tiselius HG, Zwergel U. H. Efficacy of medical expulsive treatment with Doxazosin
Medical therapy to facilitate the passage of stones: what is in pediatric patients. Urology. 2013;81:640-3.
the evidence? Eur Urol. 2009;56:455-71. 22. Aldaqadossi HA, Shaker H, Saifelnasr M, Gaber M. Efficacy
13. Pickard R, Starr K, maclennan G, Lam T, Thomas R, Burr J, and safety of tamsulosin as a medical expulsive therapy for
et al. Medical expulsive therapy in adults with ureteric stones in children. Arab J Urol. 2015;13:107-11.
colic: A multicentre, randomised, placebo-controlled trial. 23. Tasian GE, Cost NG, Granberg CF, Pulido JE, Rivera M,
Lancet. 2015;386:341-9. Schwen Z, et al. Tamsulosin and spontaneous passage of
14. Furyk JS, Chu K, Banks C, Greenslade J, Keijzers G, Thom ureteral stones in children: A multi-institutional cohort
O, et al. Distal ureteric stones and tamsulosin: A double- study. J Urol. 2014;192:506-11.
blind, placebo-controlled, randomized, multicenter trial. 24. Velazquez N, Zapata D, Hsin-Hsiao SW, Wiener JS, Lipkin
Ann Emerg Med. 2016;67:86-95.e2. ME, Routh JC. Medical expulsive therapy for pediatric
15. Meltzer AC, Burrows PK, Wolfson AB, Hollander JE, urolithiasis: Systematic review and meta-analysis. J Pediatr
Kurz M, Kirkali Z, et al. Effect of tamsulosin on passage of Urol. 2015;11:321-7.
symptomatic ureteral stones: A randomized clinical trial. 25. George A, Montag S, Cubillos J, Gitlin J, Palmer LS. The
JAMA Intern Med. 2018;178:1051-7. effect of tamsulosin on ureterolithiasis in the pediatric
16. Ye Z, Zeng G, Yang H, Tang K, Zhang X, Li H, et al. population. J Urol. 2011;185:e552-e53.
Efficacy and safety of tamsulosin in medical expulsive 26. Tian D, Li N, Huang W, Huantao Z, Zhang Y. The efficacy
therapy for distal ureteral stones with renal colic: A and safety of adrenrgic alpha-antagonists in treatment of
multicenter, randomized, double-blind, placebo-controlled distal ureteral stones in pediatric patients: A systematic
trial. Eur Urol. 2018;73:385-91. review and meta-analysis. J Pediatr Surg. 2017;52:360-65.
17. Hollingsworth JM, Canales BK, Rogers MAM, Sukumar S, 27. Scales CD, Tasian GE, Schwaderer AL, Goldfarb DS, Star
Yan P, Kuntz GM, et al. Alpha blockers for treatment of RA, Kirkali Z. Urinary stone disease: Advancing
ureteric stones: Systematic review and meta-analysis. knowledge, patient care, and population health. Clin J Am
BMJ. 2016;355(6112). Soc Nephrol. 2016 ;11:1305-12.
18. Cerwinka WH. Commentary to “Utilization of medical 28. Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-
expulsive therapy in children: An Assessment of Ciocca CJ, Matlaga BR, et al. Medical management of
nationwide practice patterns and outcomes. J Pediatr Urol. kidney stones: AUA Guideline. J Urol. 2014;192:316-24.

MEDICAL EDUCATION
Training-Module for Residents in Medical Educational Technologies

(TRIM): Need and Operational Strategies
RAJIV MAHAJAN1, PIYUSH GUPTA2 AND TEJINDER SINGH3
From Department of 1Pharmacology, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab; Department of
2Pediatrics, University College of Medical Sciences, New Delhi; and Departments of 3Pediatrics and Medical Education, Sri Guru
Ram Das Institute of Medical Sciences & Research, Amritsar, Punjab;India.

Correspondence to:DrTejinder Singh, Professor, Department of Pediatrics & Medical Education, Sri Guru Ram Das Institute of
Medical Sciences and Research, Amritsar, India. drtejinder22@gmail.com
Residents-as-teachers campaign started abroad during the last decade of the twentieth century. In India, though used informally for
teaching of undergraduate students, residents have mostly been used for patientcare and their formal induction as teacher in Indian
scenario is rare. Accordingly, not much effort has been made to train them formally in educational technologies.Teaching job
requirements of residents are not the same as that of medical college faculty; as such, a program designed for medical college faculty
will not prove equally effective for the residents. There is urgent need to train the residents in educational technologies for tapping their
full potential as teachers and for this to happen, there must be a training module, tailor-made for the teaching-job requirements of the
residents. This paper proposes such a program, after emphasizing the need of inducting residents in departmental formal teaching
activities.
Keywords:Faculty development, Educational technologies, Residents as teachers, Training module, Workshop.
V
isiting memory lane back to the days of an activities. Of course, all these figures are from other
undergraduate medical student, the first countries and no such data could be found from India.
visuals appearing in flash-back of most
Is the picture same in India? Yes, to a large extent.
medical graduate are those of clinical classes,
Residents are being used in departmental teaching
held during the evening hours, conducted by residents,
activities without being formally trained for the same in
where one used to have in-depth discussion on clinical
most of the non-clinical subjects. We don’t have a data
cases and used to finalize a work-up; where one could
for clinical subjects either, but it seems that utilization is
elicit sign and symptoms freely and in a non-threatening
suboptimal. With the introduction of competency-based
environment; where probably one was more comfortable
curriculum at undergraduate level there will be paradigm
in admitting mistakes and looking for ways to correct
shift and residents will be increasingly used for formal
them. Those sessions by residents and demonstrators
teaching activities in India without any formal training.
helped medical undergraduates immensely in honing their
Should we not have tailor-made faculty development
clinical reasoning and psychomotor skills.
activities for residents, both senior residents as well as
Residents and demonstrators are involved in routine post-graduate students, in order to tap their full potential
teaching activities in most of the departments. It has been in the conduct of the teaching activities in the
estimated that residents spend approximately 25% of their department? We are discussing some of these issues
time teaching medical students [1]. Another study found here.
that residents spent 19% of their total time in teaching
RESIDENTS AS TEACHERS
activities, with 90% of this effort devoted to teaching
associated with patient care and 10% spent in classroom Literature is full of the reasons and means of involving
teaching [2]. Even medical graduates perceive that 18% of residents-as-teachers in various medical disciplines, as
the knowledge they gained during clinical clerkships explained here.
came from residents and 13% from interns, compared with
Regulatory Obligations
25% from attending physicians and 43% from the
students’ own initiative [3]. As evident, residents have The literal meaning of word doctor is – to teach (derived
always been involved in the departmental teaching from Latin verb docere). Being christened with the title

MAHAJAN, ET AL. INVOLVING RESIDENTS IN TEACHING
‘doctor’, residents are licensed to teach. Various often quoted, ‘to teach is to learn twice.’ Being involved
regulatory bodies also make it mandatory for residents to in teaching process in the department provides residents
teach the undergraduate medical students as they are opportunities to improve their own perceived professio-
given teaching experience certificate for the same, which nal competencies. Over the time, residents have opined
is counted for career progression. As per Medical Council that teaching helps them in being good clinicians – as
of India (MCI) regulations, three-year experience as teaching stimulates critical thinking and reflection on
Junior Residents and one year experience as Senior knowledge, besides enhancing self-learning [6,7].
Resident in a recognized medical college in concerned
In another study, attending doctors expressed the
subject is necessary to be appointed as Assistant
opinion that students and residents both are benefitted
Professor [4]. Naturally residents, who are given teaching
due to teaching by residents and teaching by residents
experience, must teach as per regulatory and statutory
should be regarded as an integral part of residency
provisions.
program [8].Thus involving residents in the departmental
Institutional Requirements teaching activities improve residents’ professional and
Regulatory bodies have also mandated certain number of clinical competencies, as perceived by them.
senior and junior residents (tutors in pre- and para-clinical BENEFITS OF USING RESIDENTS AS TEACHERS
subjects) to be appointed in medical colleges in all clinical
disciplines. These staffed residents will certainly be Students often rate teaching by residents higher than
utilized for the teaching purposes of undergraduate faculty teaching; and often view residents as more
students. approachable, thus encouraging them to acknowledge
their mistakes easily and accept feedback readily [9-11].
Moreover, with the implementation of competency Residents-as-teachers also provide a kind of support
based medical curriculum in India from the admission system for the students by acting as near-peer mentors.
session 2019, it has become imperative to use the services
of residents in the teaching – as more hands are needed When residents are used as teachers, it is not only
for ‘assessment for learning’ purposes [5]. beneficial for the professional development of the
students and the residents but for the overall growth of
Refining Residents’ Own Competencies the institutions also, thus paving the way for the ultimate
Teaching is the highest form of understanding. As is improvement in patient care outcomes (Fig. 1).
Fig. 1 Beneficial effects of using residents as teacher.

NEED AND IMPACT OF EDUCATIONAL TRAINING In another study, Snell by using triangulation of data
PROGRAM FOR RESIDENTS method tried to evaluate the effectiveness of a training
program for residents-as-teachers, which included five
For generations, residents teach the way they saw their three-hour sessions. She proved that trained residents
teachers do that and imbibe skills through ‘role modeling’. had improved resident teaching skills, showed better
However, learning the art and science of teaching through application of those skills and maintained those skills
role modeling alone is not the correct and optimal way of over the academic year [17]. This is perhaps the only kind
learning; one needs to have formal experiential learning of study using data from multi-sources to establish the
through formal training. Only a formally trained resident in effectiveness of training programs for residents in
teaching technology will be motivated and dedicated educational technologies.
enough to have overall professional development. There
are many reports of formal residents-as-teachers program It is also pertinent to note that many of these
from many universities worldwide. However, considering residents would be joining medical colleges as faculty.
the unique and contextual nature of educational content Others may end up teaching DNB residents. It would thus
and environment, it may be worthwhile formulating our be a useful intervention to change the mindset towards
own program. Residents and demonstrators are usually teaching at an early stage of post-graduate career.
involved in practical demonstrations, bedside teaching
and sometimes in assessment activities like conduct of TRAINING PROGRAM - DOCUMENTED EFFORTS
objective structured clinical/practical examinations (OSCE/
OSPE). They are also increasingly being used for skill Training modules for the formal training of residents in
development in the skill labs and other simulated educational technologies and principles have been
environments. developed and implemented by various universities and
colleges, ranging from 2 hour modules to workshops for
Medical post-graduates are inherently trained to be 2-3 days to weekly / fortnightly one hour training for up to
competent in-patient care; they are not trained as ‘medical six months duration [15,16]. Longitudinal training
teachers’. Unlike requirements of having an educational programs in the form of electives for residents have also
degree in the field of humanities and arts, there is no been designed, implemented and evaluated [18-20]. In
specialized degree in the field of medicine which they most of these training programs and workshops, the most
must acquire in order to be medical teachers. This precise commonly used instruction methods were - lectures, small
reason has forced regulatory bodies to start faculty group interactive sessions and role-play. Large group
development programs in medical educational techno- interactive discussions and standardized students were
logies for the benefit of the medical faculties. In India, the least commonly used methods [21].
Medical Council of India (MCI) has developed two such
structured programs –Basic Course Workshop in Medical A literature search could retrieve very few studies
Educational Technologies and Advance Course in having used the concept of resident-as-teachers in India
Medical Education [12]. If tailor-made faculty develop- [22-24].Of these studies, only Senior Resident Training
ment programs are required to be structured for medical on Educational Principles (STEP) study has described a
faculty, the logic weighs-in on the side of structuring and structured training module in the form of workshop
implementing such a training program in educational delivered to senior residents for enhancing their teaching
technologies for residents also. skills [22]. Maharashtra University of Health Sciences
also started ‘resident as teacher’ program.[25] All such
Literature has evidence that the training improves the programs started at various institutes could not sustain
didactic, cognitive and clinical skills of the trainees [13]. for various reasons; one of them possibly being lack of
Some qualitative and quantitative studies have provided conviction about utility of such an exercise. As literature
evidence of utility of training for residents in educational shows content, structure, duration and delivery
technologies [6,14,15]. Morrison, et al. by using the variability of different workshops/training programs
Objective Structure Teaching Examination to determine designed for residents-as-teachers, with hardly any
the impact of a 13-hour teaching training program for visibility of such training modules and programs in India
residents found that compared to a control group, and as the use of residents-as-teachers is in transient
residents’ having undergone training had an overall phase in congruence with the paradigm shifts in the
improvement in teaching scores by 28% [15]. However, medical education and undergraduate and post-graduate
Dunnington and DaRosa found minimal changes in medical curriculum in India. It is imperative that a
resident teaching behavior by using OSTE, after structured training program in medical education
introducing a residents-as-teachers intervention [16]. technologies for residents’ training in India be designed.

PROPOSED TRAINING MODULE areas align well with the teaching job profile of the
residents. However, efforts must be made to sustain this
Though the need and effectiveness of a structured
training through reinforcements during residency as well
program in educational technologies for residents is self-
as during working period as faculty, as and when a
explanatory, less than 10% of residents and interns
resident joins as faculty in any institute. The description
reported to have undergone any sort of training in
of the sessions and the instructional strategies proposed
teaching. This fact alone emphasizes the need to design
for delivery of those sessions has been briefed in Web
and implement a structured program for residents-as-
Table I.
teachers, particularly tailor-made for our needs and
requirements. Due to differences in teaching-job profile,
This workshop of 22 hours can be conducted over
the structured module used for training of the medical
three days, with 30-35 residents. If three-day continuous
faculty can’t be used for the residents also.
workshop is not possible, the institute concerned can
Accordingly, a ‘Training-module for Residents’ in distribute sessions daily, as appropriate.Trained faculty
India in Medical education technologies (TRIM)’ in the members from all departments can be involved. A self-
form of workshop, based on some fundamental explanatory and most-appropriate instructional method
assumptions has been proposed here (Box 1). for the conduct of each session has been recommended;
however local factors like available infrastructure,
The goal of the proposed program is to orient the
availability of time, expertise of facilitators will ultimately
residents to the use of medical education teaching and
decide the choice of any of these methods.
assessment tools. The content of the proposed program
has been designed by extracting data from three sources
Local planners may consider adding sessions on –
– previous experience of institutes in designing and
appropriate use of multimedia, integrated teaching,
implementing such programs; MCI requirements for
assessment in integrated teaching-learning, self-directed
residents in India; and curricular mandates requiring use
learning – if their local needs direct the same. Similarly,
of residents in students’ teaching as per authors own
based upon expertise of the faculty other instructional
experiences. Three main areas identified for training and
strategies like – cine-meducation, team-based learning,
orientation of residents are – teaching principles and
team objective structured clinical examination – can be
tools, assessment and assessment tools, mentoring and
used [27-29]. One can also explore the possibility of using
teamwork.
online platforms and educational strategies for the
The training module has been structured with the delivery of the content; even partially, if not fully.
objectives of sensitizing and training residents in the Combination of synchronous and face-to-face training
concepts of – group dynamics and team-based learning, followed by asynchronous or synchronous online
small group teaching, bedside teaching, simulation based training can be a viable option in institutes with heavy
teaching and assessment, assessment of learning and patient footfall, making time constraints for residents a
assessment for learning, and mentoring. These focused real issue.
Box 1 Fundamental Assumptions for Designing Training Module for Residents

• Residents will be involved in teaching of cognitive, psychomotor and affective domains to undergraduates
(UGs) including professionalism and ethics.
• Residents will be mainly involved in interactive small group teaching and bedside teaching.
• Residents will act as role models for UGs, thereby affecting soft skills including professionalism, ethics,
communication of UGs.
• Residents will act as mentors for UGs.
• Residents will be used for assessment of UGs, of all domains, including assessment of knowledge.
• Residents will be particularly used for assessment in simulated conditions, and more for formative purposes.
• Residents will not be used for curriculum design or curriculum evaluation.

EXPECTED OUTCOMES conducting a workshop for residents will be labor

intensive; though the very incentive that the trained
What is expected to be achieved with this module? It is
residents will ultimately prove helping hands for these
not expected that with this training module the residents
faculty members for undergraduate teaching will motivate
will be fully equipped with all the teaching and
faculty to plan and conduct such teachers training
assessment tools available in the armamentarium. Only
programs for residents.
expectation is that the sensitized residents after the
training will start applying these concepts in their Residents have multiple tasks to do – patient care,
teaching activities. They are expected to be handy research, participation in continued medical education
resources as facilitators in the conduct of Objective programs including training in research methodologies;
structured clinical examination/Objective structured so tapping their full potential as teachers is a challenge in
practical examination (OSCE/OSPE) in the department. itself. Consequently, many residents might be reluctant to
After the training, they must be field-ready to act as attend teachers training program.However, owing to the
instructors in the upcoming skill labs. huge personal and professional benefits of teaching
undergraduate students, residents will get enough
It is further expected that residents teaching skills will
sensitization to attend such a training program.
evolve and will improve from ‘being novice’ to at least
‘advance beginners’. More importantly residents are The training program needs to be monitored also, at
expected to build the concept of ‘transfer of training’ at all levels, not only for continuous refinement and support
their young age as teachers and understand the utility of but also for seamless implementation. Monitoring any
having a learner-oriented educational environment in the program is a challenge in itself. Program evaluation and
institute. monitoring demands trained manpower, infrastructure,
time and coordination among different stakeholders.
PROGRAM EVALUATION
Program evaluation plan, as proposed above, will be
A detailed plan of action for program evaluation of the required to be designed, once such a program is adopted
proposed “Training-module for Residents’ in India in for implementation.
Medical education technologies (TRIM)” is out of the
CONCLUSIONS
scope of this paper. However, we are trying to issue
generalized suggestions, so that the program is evaluated There is huge man-power and potential available with us
and monitored continuously for refinement as well as for in medical institute in India in the form of junior and senior
ensuring accountability. The evaluation must include residents. Though routinely used in patient care, they
both process evaluation and outcome evaluation. While must be used as facilitators and instructors for
outcome evaluation will measure if the desired change departmental teaching and assessment activities. It is
has been achieved or not, the process evaluation will logical to assume that orientation and training of
measure how the desired change was achieved – that is if residents in the form of a workshop module will improve
the program was carried out as planned. Typically, a their acumen for teaching activities. An informed,
combination of logic and Kirkpatrick’s model will be good sensitized, oriented and trained resident will prove to be a
enough for such a program evaluation. useful and productive resource for any institute.
CHALLENGES IN IMPLEMENTING TRAINING Contributors: TS: conceptualized the paper; RM: prepared the
PROGRAM initial manuscript:PG: finalized it; All authors provided critical
inputs and approved the final manuscript.
First challenge will be to find trained faculty for the Funding: None; Competing interests: None stated.
conduct of the training program of the residents as
REFERENCES
teacher. The faculty needs to be trained themselves. The
Medical Council of India’s new guidelines, making 1. Jarvis-Selinger S, Halwani Y, Joughin K, Pratt D, Scott T,
revised basic course workshop as mandatory requirement Snell L. Supporting the development of residents as
for promotion of faculty will result in many trained faculty teachers: Current practices and emerging trends. Members
members. Faculty inertia and resistance will be the next of the FMEC PG consortium; 2011.
2. Sheets KJ, Hankin FM, Schwenk TL. Preparing surgery
big challenge in the implementation of teachers training
house officers for their teaching role. American Journal of
program for residents. The resistance is not baseless Surgery 1991;161;443-49.
even. Faculty in medical colleges is already involved in 3. Barrow MV. Medical student opinions of the house officer
multitasking – patient care, teaching postgraduates and as a medical educator. J Med Educ.1966; 41:807-10.
undergraduates, curriculum development, administrative 4. Medical Council of India. Minimum Qualification of
duties to name a few. Making arrangements and then Teachers in Medical Institutions Regulations, 1998.

Available from:https://www.mciindia.org/documents/rules Med.1998; 73:696-700.

AndRegulations/Teachers-Eligibility-Qualifications- 17. Snell L. Improving medical residents’ teaching skills. Ann R
Rgulations-1998.pdf. Accessed January 10, 2020. Coll of PhysSurg Can.1989; 22:125-28.
5. Singh T, Anshu, Modi JN. The Quarter Model: A Proposed 18. Bharel M, Jain S. A longitudinal curriculum to improve
Approach for In-training Assessment of Undergraduate resident teachingskills. Med Teach. 2005; 27:564-66.
Students in Indian Medical Schools. Indian Pediatr. 2012; 19. Mann KV, Sutton E, Frank B. Twelve tips for preparing
49:871-76. residents as teachers. Med Teach. 2007;29:301-06.
6. Busari JO, Prince KA, Scherpbier AJ, Van der Vleuten CP, 20. Weissman MA, Bensinger L, Koestler JL. Resident as
Essed GG. How residents perceive their teaching role in the teacher: educatingthe educators. Mt Sinai J Med. 2006;
clinical setting – a qualitative study. Medical Teacher 2002; 73:1165-69.
24:57-61. 21. Morrison EH, Friedland JA, Boker J, Rucker L,
7. Sheets KJ, Hankin FM, Schwenk TL. Preparing surgery Hollingshead J, Murata P.Residents-as-teachers training in
house officers for their teaching role. Am JSurg1991; U.S. residency programs and offices ofgraduate medical
161:443-49. education. Acad Med. 2001;76: S1-S4.
8. Busari JO, Scherpbier AJ, Van der Vleuten CP, Essed GG. 22. Singh S. Senior resident training on educational principles
The perception of attending doctors of the role of residents (STEP): A proposed innovative step from a developing
as teachers of undergraduate clinical students. Med Educ. nation. J EducEval Health Prof.2010;7:3 (online). Available
2003; 37:241-47. from: https://www.jeehp.org/DOIx.php?number=45.
9. Whittaker LD Jr, Estes NC, Ash J, Meyer LE. The value of Accessed February 03, 2020.
residentteaching to improve student perceptions of surgery 23. Kumar A, Agarwal D. Resident-to-resident bedside
clerkships andsurgical career choices. Am J Surg.2006; teaching: An innovative concept. Indian J Ophthalmol.
191:320-24. 2019; 67:1901-02.
10. Tolsgaard MG, Gustafsson A, Rasmussen MB, Hoiby P, 24. Ghosh SK. Resident doctors: Keystone of anatomy
Muller CG,Ringsted C. Student teachers can be as good as teaching. Clin Teach.2014; 11:461-62.
associate professorsin teaching clinical skills. Med Teach 25. Homeo Book [Page on internet]. MUHS Master of Science
2007; 29:553-57. (Health Professions Education) 2016 admission. Available
11. Ross MT, Cameron HS.Peer assisted learning: a planning from: https://www.homeobook.com/muhs-master-of-
andimplementation framework: AMEE Guide no. 30. Med science-health-professions-education-2016-admission/.
Teach.2007; 29:527-45. Accessed May 04, 2020.
12. Medical Council of India. Decisions of the council regarding 26. Wilkinson M. Team building activity – Crossing the river.
faculty development programmes. Available from: https:// Available from: https://www.leadstrat.com/leadership-
mciindia.org/CMS/wp-content/uploads/2019/10/3_MCI_ strategy-resources/team-building-activity-crossing-the-
decisions_on_MET.pdf. Accessed February 03, 2020. river/. Accessed February 04, 2020.
13. Irby DM. What Clinical Teachers in Medicine Need to 27. Kadeangadi DM, Mudigunda SS. Cinemeducation: Using
Know?Acad Med. 1994:610:333-42. films to teach medical students. J SciSoc.2019;46:73-74.
14. Khera N, Stroobant J, Primhak RA, Gupta R, Davies H. 28. Chhabra N, Kukreja S, Chhabra S, Khodabux S, Sabane H.
Training the ideal hospitaldoctor: The specialist registrars’ Team based learning strategy in biochemistry: Perceptions
perspective. Medical Education 2001; 35:957-66. and attitudes of faculty and 1st year medical students. Int J
15. Morrison EH, Rucker L, Boker JR, Hollingshead J, Appl Basic Med Res. 2017;7:72-7.
Hitchcock MA, Prislin MD, et al. A pilot 29. Amini M, Moghadami M, Kojuri J, Abbasi H, Abadi AA,
randomized,controlled trial of a longitudinal residents-as- Molaee NA, et al. Using TOSCE (Team Objective
teachers curriculum. Acad Med.2003;78:722-29. Structured Clinical Examination) in the second national
16. Dunnington GL, DaRosa D. A prospective randomized medical sciences Olympiad in Iran. J Res Med Sci. 2012;
trial of a residents-as-teachers training program.Acad 17:975-8.

WebTable I Sessions and Instructional Strategies for the Delivery of the Proposed Workshop Module for Training Residents
in Medical Education Technologies
Sessions Instructional strategies Duration (h)
Principles of group dynamics and team building Crossing the river – group activity[26] 1
Goals, roles and competencies and domains of learning and Brainstorming, interactive lecture 2
system approach
Interactive small group teaching – Problem based learning, Interactive lecture followed by group activities and reporting 3
case-based learning, tutorials, flipped classroom
Bed-side teaching, one-minute preceptor Interactive lecture, Brainstorming, Role-play 2
Simulation based teaching Hands on training in skill lab 2
Assessment: Principles and concepts Interactive lecture 1
Assessment in competency based medical education Interactive lecture, brainstorming 1
Assessment for learning, feedback and its utility Interactive lecture, brainstorming, demo 1
Assessment of knowledge – MCQs, essay (long and short) Interactive session, brainstorming, group activity 1
questions, viva-voce
Assessment of skills – OSCE / OSPE Brainstorming followed by demo and group activity 2
Work-place based assessment including assessment of Interactive lecture followed by mini-CEX demo 2
affective domain
Simulation based assessment Hands on training in skill lab 1
Mentoring: Concepts, utility and residents as role-models Interactive lecture, Brainstorming followed by group activity 3
and reporting
MCQs: Multiple choice questions; OSCE: Objective structured clinical examination, OSPE: Objective structured practical examination;
mini-CEX: Mini clinical evaluation.
INDIAN PEDIATRICS VOLUME 57__OCTOBER 15, 2020

MEDICAL EDUCATION
A Road Map for Simulation Based Medical Students Training in

Pediatrics: Preparing the Next Generation of Doctors
GEETHANJALI RAMACHANDRA,1,2 ELLEN S DEUTSCH,2,3 AND VINAY M NADKARNI2,3
From 1Krishna Institute of Medical Science Secunderabad, Telangana, India; 2Pediatric Simulation Training and Research Society
(PediSTARS), India; and 3Children’s Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, USA.
Correspondence to: Dr Geethanjali Ramachandra, Department of Pediatric Intensive Care, Krishna Institute of Medical Science,
Minister Road, Secunderabad 500 003, Telangana, India. rgeetha48@gmail.com
Current Medical training in India is generally didactic and pedagogical, and often does not systematically prepare newly graduated
doctors to be competent, confident and compassionate. After much deliberation, the Medical Council of India (MCI) has recently
introduced a new outcome-driven curriculum for undergraduate medical student training with specific milestones and an emphasis on
simulation-based learning and guided reflection. Simulation-based education and debriefing (guided reflection) has transformed medical
training in many countries by accelerating learning curves, improving team skills and behavior, and enhancing provider confidence and
competence. In this article, we provide a broad framework and roadmap suggesting how simulation-based education might be
incorporated and contextualized by undergraduate medical institutions, especially for pediatric training, using local resources to achieve
the goals of the new MCI competency-based and simulation-enhanced undergraduate curriculum
Keywords: Competency, Integration, Medical education, Undergraduate.
G
raduates, through didactic training and Team leader, Professional and Lifelong Learner”;
apprenticeships, focus on improving emphasizes collaborative and inter-disciplinary teamwork,
knowledge. However, graduates often have professionalism, respect and responsiveness to the needs of
gaps in skills, behaviors and attitudes, so the patient; limits didactic lectures to less than a third of
alternative forms of education are necessary to support total schedule; integrates communication skills training;
competence, confidence, communication skills, and and uses simulation training and guided reflection
compassion in caring for children. Entering internship
after the final year of medical school, students are The new MCI competency-based pediatric medical
required to perform many critical actions independently. graduate curriculum is based on seven core competencies
Most of the students in the Indian subcontinent learn (Box I). MCI emphasises that the teaching should be
clinical care by practicing on real patients which may aligned and integrated both horizontally (across
result in physiological and psychological harm to the disciplines in a given phase of the course) and vertically
patients and families, as well as excessive stress to the (across different phases of the course). This will allow
new graduate. Simulation is a powerful tool that can graduates to provide comprehensive care for neonates,
facilitate learning in a safe environment by deliberate infants, children and adolescents based on a sound
practice and facilitated reflection. Using simulation to knowledge of growth, development, disease and their
address individual and team skills, behaviors and clinical, social, emotional, and psychological correlates
attitudes was addressed previously in the journal [1] – we in the context of national health priorities [4]. MCI has
add to it in the light of the new MCI curriculum. directed individual undergraduate medical institutes to
form their own curriculum committees to implement
New MCI Curriculum these standards [5].
The Medical Council of India (MCI) has proposed an Can Simulation Bridge Current Gaps in Training?
exciting new initiative to revamp medical training by
creating a competency based undergraduate curriculum for The new MCI curriculum aspires to ensure that the
the Indian medical graduate [2,3]. The new curriculum medical graduate meets or exceeds global benchmarks in
focuses on Attitude, Ethics and Communication knowledge, attitudes, behaviors, skills and communi-
(AETCOM); calls for preparing students to face India’s cation abilities, and is able to provide holistic care with
health needs by training to be a “Clinician, Communicator, compassion. How do we achieve this goal?

RAMACHANDRA, ET AL. SIMULATION BASED MEDICAL STUDENTS TRAINING
Box I The New Medical Council of India hand washing, gowning and gloving, glucometer use, bag
Competency-based Pediatric Curriculum of the and mask ventilation, chest compressions, endotracheal
Indian Medical Graduate Program [4] intubation, laryngeal mask airway (LMA) insertion, basic
suturing, and episiotomy suturing. The students need to
Pediatric Competencies students must demonstrate
answer a few multiple-choice questions based on the
1. Ability to assess and promote optimal growth, information given in the SOP and video and then they are
development and nutrition of children and allowed to come for hands-on sessions. Apart from the
adolescents and identify deviations from normal. above, a simulation-based neonatal resuscitation
2. Ability to recognize and provide emergency and program (NRP) is being run for the students during their
routine ambulatory and First Level Referral Unit 6th semester. Future steps include incorporating team
care for neonates, infants, children and training and human factors in simulation. Centres such as
adolescents and refer as may be appropriate. Father Muller Simulation and Skills Centre; DY Patil
3. Ability to perform procedures as indicated for Medical Simulation Laboratory; Kasturba Medical
children of all ages in the primary care setting. College (KMC), Manipal; and GSL smart lab, Andhra
4. Ability to recognize children with special needs Pradesh have already commenced incorporating
and refer appropriately. simulation in pediatric undergraduate training.
5. Ability to promote health and prevent diseases in OVERVIEW IN OTHER COUNTRIES
children.
6. Ability to participate in National Programmes Use of simulation-based education in pediatrics is used in
related to child health and in conformation with the majority of institutions in USA [13]. SBE is based on 13
Integrated Management of Neonatal and core ‘Entrustable professional activities for entering
Childhood Illnesses (IMNCI) Strategy. residency’ from the Association of American Medical
7. Ability to communicate appropriately and Colleges [14]. Most centres in USA, Canada, United
effectively. Kingdom and New Zealand introduce simulation to
students in the first year of medical training and gradually
increase the duration and complexity from year 2
Didactic education will help the learner to gain onwards using both skill laboratories and in-hospital
knowledge, whereas simulation-based education (SBE) simulation.
will help the learner to apply their knowledge by creating
Typically, students learn various procedural skills
realistic experiences in a controlled, low risk and
(such as cannulation, blood sampling, suturing,
interactive environment. Debriefing, which is an integral
intubation, thoracentesis, aseptic precautions), history
component of the simulation experience, facilitates
taking, basic life support, airway, focussed examination,
mindful reflection, active learning, abstraction,
leadership, handover, interprofessional and family
conceptualisation, and application of theory to real
communication in simulation centres, and management
events. Integrating didactic teaching and SBE will
of emergencies with team training at hospital.
provide shorter learning curves, higher retention and
Combinations of task trainers, manikins with varying
improved behavior in future patient care encounters,
amounts of technology (low, medium, high), virtual
helping learners emerge as leaders, communicators,
reality (VR) simulations, and standardized patients (SP)
professionals and health advocates [1,6-8]. Studies have
are used for training at simulation centres. Simulation is
shown that pediatric trainees become more confident in
also used as an evaluation tool and to assess knowledge
recognising, assessing, managing sick children, and in
e.g., Objective Structured Clinical Examination (OSCE)
communicating after simulation-based training [9-12].
stations [15,16].
Progress Towards SBE in India
At the Children’s Hospital of Philadelphia (CHOP),
It is encouraging to see a few institutions in India already medical students undergo pediatric simulation training at
taking an active interest in incorporating simulation for a simulation centre at the University of Pennsylvania
undergraduate training. At the All India Institute of Perelman College of Medicine. In addition, during year 3
Medical Science (AIIMS) Delhi, and many other and 4 they undergo in situ simulation training at CHOP.
institutions, skills are taught using a blended learning Small batches of five third year students participate in
technique with both online and hands-on teaching simulation once-a-week to learn team training, neonatal
sessions. The online segment consists of a brief apnea, asthma, croup, febrile seizure, hypoglycemic
description of the standard operating procedure (SOP) seizures for 5 weeks. Similarly, fourth-year students visit
and a video of skills such as intravenous (IV) cannulation, once-a-week to learn team training, identification of sick

child, high quality resuscitation, cardiac arrhythmias,

anaphylaxis and septic shock using scripted scenarios and
high technology manikins. Debriefing normally takes
twice the time of conducting the scenario. Prior to
commencing internship, medical students participate in a
5-day intense pediatric boot camp. The boot camp is
structured to mimic real work in a Pediatric ward and
emergency room involving allied professionals such as
radiology, physiotherapy, occupational therapy, speech
therapy, child life and lactation specialists. Emphasis on
personal wellbeing in addition to skills such as PALS
emergencies and handoff communication has made this
boot camp a great success [11,17]. CHOP is also helping
overseas centres conduct team training and debriefing
through tele-simulation.
WHAT IS NEEDED FOR SIMULATION-BASED
TRAINING?
To succeed in our mission to provide SBE, we need Fig. 1 Designing a simulation program.
commitment by the faculty and administration, a clear
roadmap, passion to succeed and, willingness to invest simulations, procure manikins and other equipment, train
for our new generation of young doctors. Now that the personnel, design curricula and script scenarios. Ongoing
need for SBE has been identified [2-5], next steps will be research and feedback to refine the curriculum will lead
to develop faculty, secure funding, identify space for to high quality training (Fig. 1 and 2).
Needs Assessment: Why? Identify gaps in training, potential benefits
Resource development: Sim centre, In situ Auditorium/

Faculty development: Who, when where how?
Classroom, Standardized patient, Virual Reality
Funding ↓ Equipment, Personnel
Curriculum Design: Goals, type of simulation, number of trainees & trainers, manikin, duration
Scenario Scripting: Title, learning objectives, case history, additional background information, manikin, moulage,
props, actors, scenario flow, debriefing script
Faculty rehearsal
↓ Identify missing objects
Simulation Delivery: Prebrief (manikin, psychological safety, suspension of disbelief), conduct scenario.
Observe and Debrief / Repeat if needed.

Refine scenario with feedback
Summarise learning
Program Evaluation: Did the learniners like it? Did they learn?
Did it make difference to patient outcome?
Fig. 2 A road map for integrating simulation in medical education.

Faculty development: This is the most vital part of a Delivering simulation: Prebriefing for psychological
simulation program. There are 2 or 3-day simulation safety of the learners, introduction of the environment,
faculty development courses available, emphasizing parameters of simulation, capabilities of manikin, and
curriculum development and debriefing followed by suspension of disbelief about manikin is the key to
ongoing audit and mentorship. facilitate learning during formative simulations. For
immersive simulation, it is desirable that room should
Access to resources: Funding, identifying space,
match the clinical area and instructors stay out of sight of
manikins, audio-visual aids, appropriate equipment to
the learners during the scenario. Appropriate audio-visual
create a realistic patient-care environment, an enclosed
aids add realism to the scenario [18,19].
observation room, debriefing room and personnel to
manage the program are some of the resources required Debriefing: This is the heart of simulation and converts
for a successful simulation program. experience into learning. Learners are guided by a
Curriculum design: SBE design involves appropriate facilitator to reflect on their actions, reinforce correct
needs analysis, clearly defined objectives, selection of responses, and plan for better performance. There are
the type of simulation, descriptions of learner and various types of debriefing techniques, including direct
trainers, determination of place (simulation laboratory/in feedback, plus delta, pause and debrief, rapid cycle
situ/other), identification of most appropriate simulation deliberate practice (RCDP) and advocacy inquiry [20-22].
modality, decision about the duration of simulation, Studies have shown that scripted debriefing might be more
contextualized and validated evaluation tools, and any beneficial to novice faculty [23]. Attention is focused not
assessment needed. It is important to have specific and only on ‘what could be improved’ but also ‘what went well’,
measurable objectives [17-19]. and often asks learners to develop their own insights into
‘why’ processes went well or needed improvement.
Scenario development: It involves scripting the scenario
with a title, learning objectives, case history ‘stem’ to be Research, feedback and refinement: Research into the
told to the learners, manikin, props and moulages needed, program to measure the impact of training and ongoing
additional background information for facilitators, feedback to refine the curriculum and scripts are key for a
scenario flow and debriefing script. successful simulation program, but must be carefully
SP: Standardized patient; BLS: Basic life support; VR: Virtual reality; IV: Intravenous; IO: Intra osseous; LP: Lumbar puncture; RCDP: Rapid cycle
deliberate practice [21].
Fig. 3 A guide to integrate simulation for pediatric medical students.

Table I Suggested Solutions for Overcoming Barriers to Implement Medical Student Simulation
Faculty Training
• Create a central body to govern undergraduate medical simulation
• Collaborate with national and international simulation societies such as the All India Institute of Medical Science (AIIMS),
International Pediatric Simulation Society (IPSS), International Network for Simulation-based Pediatric Innovation, Research
and Education (INSPIRE)
• Implement tele-simulation with centres pioneered in simulation program.
• Provide incentives to faculty who become simulation facilitators - promotions, decreased clinical responsibilities
Curriculum development and scenarios
• Pilot in apex institutions and share curriculum with other institutions
• Collaborate with international bodies
• Create a pool of scenarios to be banked
• Develop national conferences on medical simulation, to bring together all trainers
Cost
• Pool resources. There are many large simulation labs which are not fully utilized
• Encourage realistic low-cost simulation
• Utilise Virtual reality, in situ and Standardised patient simulation modalities
• Develop 3-Dimensional printing and silicone casting
• Conduct research into developing indigenous low-cost high technology manikins
• Reserve high-cost manikins for specific learning circumstances
Large number of students, limited time
• Use classrooms for didactics followed by simulation so students can take turns learning by observation as well as participation.
• Encourage Virtual Reality
• Develop a library of simulation scenarios that can be re-used, so that subsequent simulation development takes less time
Research
• Form a national central governing body to supervise, encourage and fund simulation research
• Collaborate with organizations already working in this field like INSPIRE, SSH, PediSTARS.
• Publish national medical student simulation education journals
INSPIRE:International Network for Simulation-based Pediatric Innovation, Research and Education; SSH: Society for Simulation in Healthcare;
PediSTARS: Pediatric Simulation Training and Research Society.
implemented to preserve psychological safety for and communicating effectively with families. Other
learning. competencies can be gradually integrated as a multistep
A Framework to Implement Simulation-based- process. Simulations such as history taking, airway
training in Pediatrics management, basic life support (BLS), lumbar puncture,
newborn examination, and nutritional assessment can focus
MCI 2018 guidelines describe several competencies in on individual learning. However, emergency scenarios
the pediatric curriculum for medical students [4]. A such as management of respiratory distress, cardiac arrest,
stepwise approach starting with simpler skills in year 1, septic shock, and seizures, and dealing with challenging
and adding more complex skills and scenarios in families should be conducted as team training exercises so
subsequent years would allow learners to build on skills students can also develop skills in leadership, role
they have developed (Fig. 3). This will also allow trainers allocation, calling for help, resource utilisation and
with specific skill sets to support skill training and reserve providing clear instruction to colleagues [20].
highly trained simulation educators for more complex
simulation scenarios. Challenges
It is desirable to start with the highest priority Faculty comfort will be a major challenge, because of the
competencies, such as identifying a sick child, performing huge volume of students, the need for specialized training
basic procedures such as cannulation, intraosseous (IO) in simulation and a lack of time. Faculty development,
access, handwashing, aseptic precautions, waste disposal, manikin availability, cost, and access to space can be a

burden unless management and infrastructure support is Simulation, University of Leicester, UK; Jane Torrie, Faculty of
available. Psychological safety for the students is Medical and Health Sciences, University of Auckland, New
extremely important to ensure learning from simulation, Zealand.
and this also applies to faculty who are developing their Contributors: GR: reviewed the literature, drafted and finalized
the manuscript. ED, VN: reviewed, revised and finalized the
own simulation skills. Without psychological safety, both
manuscript.
the learner and the program may be damaged. Funding: None; Competing interests: None stated.
Overcoming Barriers REFERENCES
A previous publication [1] called for exploring and 1. Kalaniti K, Campbell DM. Simulation-based medical
embracing SBE in Indian subcontinent. After 4 years, it is education: Time for a pedagogical shift. Indian Pediatr.
exciting to witness incorporation of simulation by MCI in 2015;52:41-5.
undergraduate curriculum and watch the breakthrough 2. Medical Council of India. Competency based
happening at some of the leading institutions in India. Undergraduate Curriculum for the Indian Medical
Graduate, 2018. Vol 1, pages 1-251. Available from:
India is one of the most cost-effective countries when it
https://www.mciindia.org/CMS/wp-content/uploads/2019/
comes to healthcare [24]. It is only a question of time for 01/UG-Curriculum-Vol-I.pdf. Accessed August 31, 2019.
SBE to be applied across the country in medical 3. Medical Council of India. Competency Based Assessment
education. Module for Undergraduate Medical Education Training
Program, 2019: pages 1-30 Available from: https://
Creating a pool of highly trained faculty, optimizing
mciindia.org/CMS/ wpcontent/uploads/2019/10/Module_
low cost simulation opportunities, sharing resources, Competence_based_02.09.2019.pdf. Accessed August 31,
combining simulation with didactic classroom lectures 2019.
[25,26], encouraging development of 3D printing, virtual 4. Medical Council of India, Competency based
reality [27], collaborating with simulation training Undergraduate curriculum for the Indian Medical
organizations [28-30], and research into the impact of Graduate, 2018. Vol II – Pediatrics: pages 150-201.
high-quality simulation-based training are some of the Available from: https://www.mciindia.org/ CMS/wp-
answers. Indian students deserve the best education content/uploads/2019/01/UG-Curriculum-Vol-II.pdf.
platforms. Table I provides some insights into how we Accessed August 31, 2019.
5. Medical Council of India, Curriculum Implementation
can make substantial progress.
Support Program of the Competency Based Undergraduate
CONCLUSION Medical Education Curriculum 2019. p. 1-188.
6. So HY, Chen PP, Wong GKC, Chan TTN. Simulation in
It is now time for the much-needed paradigm shift – the medical education. JR Coll Physicians Edinb. 2019;
time to incorporate simulation in medical education 49:52-7.
countrywide. It is no longer acceptable for our medical 7. Okuda Y, Bryson EO, DeMaria S Jr, Jacobson L, Quinones
students to learn and practice on real patients, without first J, Shen B, et al. The utility of simulation in medical
learning and training on simulated patients and situations. education: what is the evidence? Mt Sinai J Med. 2009;
Simulation will never replace learning based upon 76:330-43.
8. Cheng A, Lang TR, Starr SR, Pusic M, Cook DA.
exposure to real patients but will increasingly supplement
Technology-enhanced simulation and pediatric education:
and augment medical education in India. We need to think A meta-analysis. Pediatrics. 2014;133:e1313-23.
differently and be constructively disruptive as we develop 9. Ooi A, Hambidge J, Wallace A. Developing an
simulation-based medical student curricula. The cost of undergraduate paediatric simulation workshop in a
integrating simulation into medical student education is resource constrained setting: A practical ‘how to’ guide. J
modest compared to the potential number of lives saved Paediatr Child Health. 2019;55:737-42.
and the joy of learning provided to our new generation of 10. Morrissey B, Jacob H, Harnik E, Mackay K, Moreiras J.
caring, able, deserving, and intelligent doctors. Simulation in undergraduate paediatrics: A cluster-
randomised trial. Clin Teach. 2016;13:337-42.
Acknowledgements: Ashok Deorari, All India institute of 11. Pete Devon E, Tenney-Soeiro R, Ronan J, Balmer DF. A
Medical Science, Delhi. India; Rashmi Ramachandran, All India pediatric preintern boot camp: Program development and
Institute of Medical Science, Delhi, India; Adam Cheng, evaluation informed by a conceptual framework. Acad
KidSIM Simulation Program, Alberta, Canada; Gregg Lipschik, Pediatr. 2019;19:165-9.
Life Support Training and Undergraduate Curriculum 12. Stone K, Reid J, Caglar D, Christensen A, Strelitz B, Zhou L,
Simulation at Penn Medicine Philadelphia, USA; Erin Pete et al. Increasing pediatric resident simulated resuscitation
Devon, The Children’s Hospital of Philadelphia, University of performance: A standardized simulation-based curriculum.
Pennsylvania. USA; Harsh Bhoopatka, Clinical Skills Centre, Resuscitation. 2014;85:1099-105.
University of Auckland New Zealand; Evan Sanders, Harvard 13. Vukin E, Greenberg R, Auerbach M, Chang L, Scotten M,
Medical School. USA; Malcolm Smith, Department of Tenney-Soeiro R, et al. Use of simulation-based education:

A national survey of pediatric clerkship directors. Acad 22. Rudolph JW, Simon R, Dufresne RL, Raemer DB. There’s
Pediatr. 2014;14:369-74. no such thing as “nonjudgmental” debriefing: A theory and
14. Association of American Medical Colleges (AAMC). Core method for debriefing with good judgment. Simul Healthc.
entrustable professional activities for entering Residency: 2006;1:49-55 .
Toolkits for the 13 Core EPAs. Jan 2017. p. 1-20. Available 23. Cheng A, Hunt EA, Donoghue A, Nelson-McMillan K,
from: https://www.aamc.org/system/files/c/2/484778- Nishisaki A, Leflore J, et al. Examining pediatric
epa13toolkit.pdf. Accessed August 31, 2019. resuscitation education using simulation and scripted
15. Nadkarni LD, Roskind CG, Auerbach MA, Calhoun AW, debriefing: A multicenter randomized trial. JAMA Pediatr.
Adler MD, Kessler DO. The development and validation of 2013;167:528-3.
a concise instrument for formative assessment of team 24. Govindarajan V, Ramamurti R. India’s secret to low-cost
leader performance during simulated pediatric resuscita- health care. Harvard Business Review. Available from:
tions. Simul Healthc. 2018;13:77-82. https://hbr.org/2013/10/indias-secret-to-low-cost-
16. Ryall T, Judd BK, Gordon CJ. Simulation-based healthcare. Accessed August 31, 2019.
assessments in health professional education: A systematic 25. Fitch MT. Using high-fidelity emergency simulation with
review. J Multidiscip Health. 2016;9:69-82. large groups of preclinical medical students in a basic
17. Hartke A, Pete Devon E, Burns R, Rideout M. Building a science course. Med Teach. 2007;29:261-3.
boot camp: Pediatric residency preparatory course design 26. Heitz C, Brown A, Johnson JE, Fitch MT. Large group
workshop and tool kit. MedEdPORTAL. 2019;15:10860. high-fidelity simulation enhances medical student learning.
Available from: https://doi.org/10.15766/mep_2374- Med Teach. 2009;31:e206-10.
8265.10860. Accessed August 31, 2019. 27. Vincent DS, Sherstyuk A, Burgess L, Connolly KK.
18. Cheng A, Duff J, Grant E, Kissoon N, Grant VJ. Simulation Teaching mass casualty triage skills using immersive three-
in paediatrics: An educational revolution. Paediatr Child dimensional virtual reality. Acad Emerg Med. 2008;
Health. 2007;12:465-8. 15:1160-5.
19. Lopreiato JO, Sawyer T. Simulation-based medical 28. International Network for Simulation-based Pediatric
education in paediatrics Acad Pediatr. 2015;15:134-42. Innovation, Research and Education (INSPIRE). Available
20. Roussin CJ, Weinstock P. SimZones: An organizational from: http://www.inspiresim.com/. Accessed August 31,
innovation for simulation programs and centers. Acad 2019.
Med. 2017;92:1114-20. 29. International Pediatric Simulation Society (IPSS).
21. Hunt EA, Duval-Arnould JM, Nelson-McMillan KL, Available from: http://ipssglobal.org/. Accessed August
Bradshaw JH, Diener-West M, Perretta JS et al. Pediatric 31, 2019.
resident resuscitation skills improve after ‘‘rapid cycle 30. Society for Simulation in Healthcare. Available from:
deliberate practice’’ training. Resuscitation. 2014;85:945-51. https://www.ssih.org/. Accessed August 31, 2019.

Reminiscences from Indian Pediatrics: A Tale of 50 Years
Half a Century With Pediatric Viral Encephalitis

ROMIT SAXENA* AND ANNESHA CHAKRABORTI
Department of Pediatrics, Maulana Azad Medical College.
*drromit@gmail.com
Periodic outbreaks of acute encephalitis regularly occur presented with meningoencephalitis, from erstwhile
across India, leading to substantial mortality [1]. Japanese Bombay. Infectious etiological agents reported, included
encephalitis (JE) has been the leading cause for the same coxsackie (B4/B6) (12.8%), and echovirus (19/21)
[2,3], but the incidence of non-JE etiologies has been (12.8%). Their patient population had fever (91.2%, 45.8%
steadily increasing as well [1,4]. Even half a century back, high grade), altered sensorium (98/125) and convulsions
pediatricians were struggling with this (91/125) (1/3rd had persistent seizures).
disease entity. We came across two They observed that both presence of
articles from Indian Pediatrics archives meningeal signs and absence of
dating back to 1970, and endeavor to altered sensorium were associated with a
describe the change in epidemiology better prognosis. They also defined a
and approach to viral encephalitis, over unique entity, acute fulminant
the past five decades. meningoencephalitis (AFE)
(disturbance in sensorium within 24
THE PAST
hours of onset), which was associated
Soon after Independence, there were with terminal outcome.
many outbreaks of acute encephalitis in
Since then, acute encephalitis,
India. In 1954, Dr. Khan, while working
predominantly attributed to Japanese
at Tata Main hospital, Jamshedpur,
encephalitis, has been reported from
described an epidemic, from Uttar
almost all states in India [3].
Pradesh, Bengal and Bihar, of an acute
Enteroviruses [7,8] and Kyasanur forest
encephalitic disease process, that
disease [7] have also resulted in several
predominantly affected children and
outbreaks since independence.
had a high mortality rate. He undertook this work with Dr.
Seal (Kolkata) and Dr. Work (Pune) [5,6]. This was the first THE PRESENT
reported epidemic of encephalitis from India.
This disease rattles the best brains even today. Worldwide,
Indian pediatricians have always been intrigued by this AES incidence varies between 3.5 and 7.4 per 100,000
disease entity. During 1966-68, Balakrishnan, et al. [7] patient-years [9]. But the mortality rate, has fortunately
came across 72 consecutive pediatric cases of viral come down, to around 6% (National Vector Borne
encephalitis. They published their experience in the April, Diseases Control Programme (NVBDCP,2018) [3].
1970 edition of Indian Pediatrics [9]. They presented a
Across half a century, the etiology of AES is still
case series of 19 clinically diagnosed pediatric viral acute
predominantly viral. JE has continued to remain active,
encephalitis syndrome (AES) from Pondicherry.
with recent outbreaks in Malkangiri [2012], Manipur
Cerebrospinal fluid examination was normal in a third of
(2016) and Delhi (2011) [10]. Amongst non-JE etiologies,
their cases, while echovirus-7 was isolated from CSF in
enteroviruses (EV-71, coxsackie, echoviruses) [11,12],
37% cases. Treatment offered by them 50 years back, was
Nipah [13], Chandipura [14] and even dengue virus [12]
quite similar to what we offer today, including rehydration,
are on the rise. Herpes simplex virus (HSV), the
nutrition by intravenous/enteral routes (nasogastric),
commonest cause of sporadic encephalitis worldwide, is
antibiotics (tetracycline) and corticosteroids. But
still not as common in India [15]. Non-infectious causes
unfortunately, their mortality rate was quite high (79%).
have also been identified, as due to consumption of plant
Later, the same year (October, 1970), Athavale, et al. toxins (seeds of Cassia occidentalis, Cassia beans)
[8] published their experience with 125 children, who (kasondi plant associated acute hepatomyoencephalopathy

A TALE OF 50 YEARS ACUTE VIRAL ENCEPHALITIS
[16] and litchi fruits (containing hypoglycin A and MCPG) RR. Clinico-epidemiological study of viral acute
(Muzaffarpur encephalitis) [17]. encephalitis syndrome cases and comparison to nonviral
cases in children from Eastern India. J Glob Infect Dis.
Pinpointing an etiological agent for acute encephalitis 2019;11:7-12.
continues to be challenging, and may remain inconclusive 2. Directorate of National Vector Borne Disease Control
in many cases. A detailed history, thorough physical Programme- Delhi. State wise number of AES/JE cases and
examination focusing on level and localization of brain deaths from 2014-2020 (till April); Available from: https:
function, laboratory investigations, especially lumbar // nvbdcp.gov.in/WriteReadData/l892s/819485739158866
puncture, are very important in the treatment of the disease 1482.pdf. Accessed on June 4, 2020.
3. Ministry of Health and Family Welfare (MoHFW), Govern-
[15]. Nowadays, techniques such as enzyme-linked
ment of India. Acute encephalitis syndrome: National health
immunosorbent assay, molecular techniques like portal. Centre for Health Informatics (CHI), National
polymerase chain reaction (PCR) and dot blot Institute of Health and Family Welfare (NIHFW); 2019.
hybridization are being increasingly used [18]. 4. Kakoti G, Dutta P, Ram Das B, Borah J, Mahanta J. Clinical
Advancement in radiological imaging has tremendously profile and outcome of Japanese encephalitis in children
helped clinical decision making. Computed tomography admitted with acute encephalitis syndrome. Biomed Res Int.
scans in emergency situations, and magnetic resonance 2013:152656.
imaging when patients are more stable (especially with a 5. Khan N. Jamshedpur fever: A preliminary report. Indian J
diffusion weighted imaging and a gadolinium enhanced Med Sci. 1954;8:597.
6. Khan N. Jamshedpur fever and Reye’s syndrome. JAMA.
study), can help identify cerebral edema, and point towards
1983;250:1025.
a specific diagnosis. 7. Balakrishnan S, John E, Madhavan HN. Echo-Virus
Since viral encephalitis has a substantially high mor- encephalitis in Pondicherry. Indian Pediatr. 1970;7:212-8.
bidity and mortality rate, primary prevention through im- 8. Athavale VB, Desai NN, Kadoth KK, Aiyer RR. Acute viral
munization, holds a far greater promise than targeted meningoencephalitis. Indian Pediatr. 1970;7:547-56.
9. Granerod J, Crowcroft NS. The epidemiology of acute
therapy after disease infliction. Subsequent to the longest
encephalitis. Neuropsychol Rehabil. 2007;17:406-28.
epidemic of JE in Gorakhpur (2005), mass vaccination 10. Kulkarni R, Sapkal GN, Kaushal H, Mourya DT. Japanese
against the same was introduced in endemic districts [10]. Encephalitis: A brief review on Indian Perspectives. Open
NVBDCP, launched in 2003-4, focusses on training staff at Virol J. 2018;12:121-30.
ground level (PHCs and CHCs) for early diagnosis and 11. Joshi R, Kalantri SP, Reingold A, Colford JM. Changing
management. It also focusses on source reduction, espe- landscape of acute encephalitis syndrome in India: a
cially vector control measures as water and hygiene prac- systematic review. Natl Med J India. 2012;25:212-20.
tices, fogging, space spraying and antilarval measures [3]. 12. Ravi V, Mani R, Govekar S, Desai A, Lakshman L,
Ravikumar B. Aetiology and laboratory diagnosis of acute
THE FUTURE encephalitis syndrome with special reference to India. J
Commun Dis. 2014;46:12-23.
Newer techniques as matrix-assisted laser desorption
13. S PM. Nipah virus in India: Past, present and future. Int J
ionization time-of-flight mass spectrometry (MALDI-TOF Community Med Public Health. 2018;5:3653-58.
MS), unbiased high-throughput sequencing (HTS) and 14. Sapkal GN, Sawant PM, Mourya DT. Chandipura Viral
VirCapSeq-VERT (virome capture sequencing for Encephalitis: A brief review. Open Virol J. 2018; 12:44-51.
vertebrate viruses) may hold promise for the future, in 15. Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishtha
providing accurate and rapid epidemiological and VM, et al. Consensus guidelines on evaluation and
virological data for acute meningoencephalitis patients management of suspected acute viral encephalitis in
[20,27]. More research is still needed for development of children in India. Indian Pediatr. 2012;49:897-910.
more robust vaccines with improved immunogenicity. 16. Vashishtha VM, Kumar A, John TJ, Nayak NC. Cassia
occidentalis poisoning as the probable cause of
Further strengthening of NVBDCP programs and
hepatomyoencephalopathy in children in western Uttar
surveillance measures will contribute towards controlling Pradesh. Indian J Med Res. 2007;125:756-62.
arboviral encephalitis. 17. Shrivastava A, Kumar A, Thomas JD, Laserson KF,
Though, over past half century, we have progressed and Bhushan G, Carter MD, et al. Association of acute toxic
reduced case fatality, the basic tenets of medicine, a good encephalopathy with litchi consumption in an outbreak in
Muzaffarpur, India, 2014: A case-control study. Lancet
clinical history, and detailed serial neurological
Glob Health. 2017;5:e458–66.
examinations and testing as CSF examination, remain the 18.Cobo F. Application of MALDI-TOF mass spectrometry in
backbone for treating viral meningoencephalitis. clinical virology: A review. Open Virol J. 2013;7:84-90.
REFERENCES 19. Kennedy PGE, Quan P-L, Lipkin WI. Viral encephalitis of
unknown cause: current perspective and recent advances.
1. Tripathy SK, Mishra P, Dwibedi B, Priyadarshini L, Das Viruses. 2017;9:138.

UPDATE
Identification, Evaluation, and Management of Children With Autism

Spectrum Disorder: American Academy of Pediatrics 2020 Clinical
Guidelines
SHARMILA BANERJEE MUKHERJEE
From Department of Pediatrics, Kalawati Saran Children’s Hospital, New Delhi, India.
Correspondence to:Dr. Sharmila B. Mukherjee, Department of Pediatrics, Kalawati Saran Children’s Hospital, New Delhi. India.
theshormi@gmail.com
The American Academy of Pediatrics recently published clinical guidelines for evaluation and management of children and adolescents
with Autism Spectrum Disorder (ASD), nearly 12 years after the previous version. This article outlines salient features, highlights
significant differences from the 2007 version, and discusses implications for Indian professionals dealing with affected families.
Keywords: Dignostic tools, Investigations, Neuroimaging, Screening.
T
he American Academy of Pediatrics (AAP) etiopathogenesis remains uncertain [1]. Earlier diagnosis is
recently released clinical guidelines for the more common in higher socio-economic strata who have
evaluation and management of children and better access to services, while later identification is
adolescents with autism spectrum disorder associated with milder manifestations. Clinical symptoms
(ASD) [1]. The previous 2007 guidelines covered both include core symptoms and co-existing conditions
separately [2,3]. Many changes have occurred over the (medical, genetic, neuro-developmental, psychiatric and/or
last 12 years: increasing prevalence; revised nomen- behavioral), the cumulative effect of which influence extent
clature and diagnostic criteria of Diagnostic and of social and functional impairment. The guidelines
Statistical Manual of Mental Disorders, fifth edition described these in-depth. They also emphasize the need
(DSM-5) [4,5]; greater understanding of clinical profile for holistic evaluation and management to achieve best
[6], neurobiology and etiopathogenesis; advances in possible outcomes.
genetic testing [7]; evidence-based interventions; and a
paradigm shift to family-centred therapy and holistic SCREENING AND DIAGNOSIS
management throughout life. Understandably, there was The USA health system practices universal
a strong need for an update. developmental surveillance with ASD-specific screening
The increasing worldwide prevalence of ASD means at 18 and 24/30 months. Earlier screening is indicated in
primary care service providers (PCP) and pediatricians high-risk individuals or when red flags for ASD are
will encounter ASD routinely. Not only should we be identified. Suspicion or parental concerns warrant in-
competent enough to recognize, evaluate and establish depth evaluation. Establishment of diagnosis is primarily
diagnosis, we should be empowered to counsel, help clinical, based on parental interview, personal
families in decision making, and provide continual observations and DSM-5 criteria. Though diagnostic
support. After outlining salient features of the 2020 tools are not mandatory, they help in extracting clinical
guidelines and highlighting differences from the last one information. Structured evaluation of behaviour,
(Tables I and II), implications for Indian professionals will cognition, language, adaptive function, motor function,
be discussed. hearing, vision and sensory processing is recommended.
Diagnoses established by the aforementioned compre-
Previously, increasing prevalence was attributed to hensive assessment in children under 30 months remain
growing awareness, improving surveillance and less stable in ≥80% in adulthood.
misdiagnoses [2]. The present status (1in 59) of ASD in the
US is also probably due to broadening of phenotype by Etiologic evaluation comprises of detailed history-
DSM-5, universal surveillance and increased availability taking and examination (anthropometry, dysmorphism,
of services. Whether biological risk factors contribute to skin, neurologic and systemic). The indications for

UPDATE AUTISM SPECTRUM DISORDER
Table I American Academy of Pediatrics Guidelines for Autism Spectrum Disorder (ASD)
Identification and evaluation; AAP, 2007 [2] Identification, evaluation and management; AAP, 2020 [1]
Clinical symptoms
Cognitive impairment in 50%. Secondary ASD (10%) due to Cognitive impairment and minimally verbalin 30% each.
medical/genetic or environmental factors (more when severe Additional co-morbidities, other developmental/psychiatric
delay and dysmorphism). Co-morbid conditions: seizures, (ADHD, motor coordination disorder, anxiety, mood disorders)
gastrointestinal and sleep disorders, and challenging behaviors. and behavioral disorders (food refusal, pica, self-injury and
aggression).
Screening and diagnosis
Developmental surveillance existed, but few (8%) PCP practiced Surveillance increased (75%). M-CHAT-R/FU used. Tools
it. M-CHAT used. listed for younger ages.
Clinical diagnosis by DSM-4. Focus on category of severity, Clinical diagnosis by DSM5. ADI-R, ADO-S, CARS-2, SCQ
functional impairment & etiology (mainly by experts). and SRS may be used. Evaluation (see text) by PCP and experts.
Etiologic evaluation
• High resolution karyotype; • Discuss chromosomal microarray;
• DNA tests for FXS in all cases with GDD/ID; • Discuss tests for Fragile X Syndrome;
• MECP2 analysis in Rettsdisorder. • Consider MECP2 sequencing, if applicable
• Consider WES and genetic referral.
Recurrence rate 2-8% in idiopathic ASD, higher/lower in Empirical, 4-14% if one previously affected child, 32-36%
secondary ASD. if ≥2 affected children.
Prepared from Hyman, et al. [1] and Johnson, et al. [2].ADHD Attention deficit hyperactivity disorder; ADI-R Autism diagnostic inventory-
revised; ADOS-2 Autism diagnostic observation schedule, 2nd edition; CARS-2 Childhood autism rating scale, 2ndedition;, M-CHAT:
Modified checklist for autism in toddlers, R/F Revised with follow-Up;MECP2: Methyl CpG-binding protein 2; SCQ: Social Communication
Questionnaire; SRS: Social responsiveness scale; WES: Whole exome sequencing.
magnetic resonance imaging (MRI), electroencephalo- of which is still low) are given in greater detail.
graphy (EEG) and metabolic testing remain individualized,
Evaluation of maladaptive behavior and psychiatric
with provision of more details. Genetic evaluation is
conditions are separate and described with respect to the
recommended in all. The advantages of establishing
atypical development of ASD. The psychopharmacology
genetic etiology include accuracy in counselling,
section details principles of prescription and lists
possible specific therapy, avoiding unnecessary testing,
medications according to behavior-symptom cluster. The
and increased family acceptance.
emerging role of psycho-pharmacogenetic testing is
Interventions mentioned. According to the new guidelines, if a family
opts for CAM, safety and effectiveness requires
The goals remain minimizing core deficits, eliminating
monitoring.
maladaptive behaviour, and maximizing functional
independence. Intervention should be “individualized, Working with Families
developmentally appropriate and intensive” [1]. Periodic
The USA‘Medical home’ model for primary care aims at
documentation of performance is required for monitoring
“accessible, continuous, comprehensive, family centred,
response. The caveat that all interventions should be
coordinated, compassionate, and culturally sensitive
evidence-based has been added, with enumeration of
health care for all children and youth, including those with
characteristics of effective intervention.
special needs” [8]. Though recommended for ASD since
Some sections i.e., models of early intervention and 2007, the process was not well-defined. The latest
education, psychopharmacology and complementary guidelines aim at better PCP and caregiver partnership,
alternative therapy (CAM) are quite technical, since the revolving around shared decision-making. Resources
basics were extensively explained in the previous have been developed for pediatricians to enable them to
guidelines. Hence, non-experts may not understand them deal with emerging issues, counsel effectively, provide
unless they read the earlier version. Management of parents with information and direct them towards advocacy
medical conditions, social skill instruction, speech and and support groups. It is envisioned that this will result in
language therapy, motor therapy (including occupational easier handling of challenges, smoother transitions during
therapy) and sensory therapies (the supportive evidence adolescence (higher education/vocation, sexuality) and

Table II American Academy of Pediatrics Guidelines for Autism Spectrum Disorder (ASD)
Management; AAP, 2007 [3] Identification, evaluation and management; AAP, 2020 [1]
Interventions
Principles, components and curricula used in early intervention This continues without alluding to the basics and hence may
are well explained. appear more technical.
Educational models have been named but not explained. More details are presented. Emphasis is on classroom models,
Differences between programs by age (younger vs older) given. less restrictive settings and development of social skills.
Speech and language approaches named but not explained. Details of language behavior and techniques included.
Brief mention of occupational and sensory therapy. Stress given to developing skills for conversing. Motor
component new.
Management of concurrent medical conditions like seizures, Management of feeding disorders, obesity, pica, dental health,
gastrointestinal symptoms and sleep problems detailed wandering and motor disorders have been added
Challenging behaviors were included as a sub-group of medical Behavioral and psychiatric disorders well described.Screening
problems and also in the section of psycho-pharmacology. for behavioral and emotional problems (including depression >
12 y) advised.
Clinical approach to psycho-pharmacology explained step-wise. Focus is on principles of prescription and drugs listed by
behavior-symptom cluster.
CAM categorized as biological and non-biological groups CAM grouped as natural products, mind and body practices,
and others
Working with families
PCP responsibilities include provision of longitudinal support Approaches have been devised at various levels for capacity
to families, handling crises, providing emotional support and building of PCP and promotion of professional-family
referring them for counselling, medical and/or mental health partnership to provide patient and family centered care as well
services if required. as promoting research.
Research and service needs
Not included in the previous guidelines Seven broad research areas identified
Prepared from Hyman, et at. [1] and Myeos, etal. [3]. CAM: Complementary alternative medicine; PCP: primarycare service provider.
adulthood (employment readiness, medical care, legal expert bodies [9,10] sensitize professionals, but do not
guardianship and living arrangements), and better focus on capacity-building.
understanding of ASD related rights and laws.
Given these challenges, the provision of easily
Research and Service Needs accessible, family centred, individualized and intensive,
multi-disciplinary intervention according to these
Key areas identified to direct focus of funding include,
recommendations (but tailored to Indian settings) to all
basic and translational science (genetics, epigenetics,
affected families is still a distant goal. The need of the
neurobiology, psychopharmacology), clinical trials for
hour is planning and implementing evidence-based
focussed interventions, epidemiological surveillance and
concrete strategies that will enable professionals dealing
implementation research for health care services.
with ASD to provide global standards of care to these
Implications for the Indian Setting children and their families.
These guidelines have brought our existing lacunae to Quality improvement, collaboration and integration is
the forefront. Few pediatricians routinely practice required among the health, education, social welfare and
developmental surveillance. Though DSM-5 and public health systems to provide evidence-based,
indigenous Indian tools are used for diagnosis, and universal care to children/adolescents and families
intervention centres have been established all over the affected by ASD. The 2020 guidelines outline strategies
country, there is wide variability in skills and availability for capacity building of PCP to support this vulnerable
of multi-disciplinary professionals dealing with ASD, population from suspicion of ASD, through diagnosis
inconsistency in practice protocols, and minimal quality and service provision, to adulthood.
checking. National Trust workshops are infrequent and
REFERENCES
primarily related to disability certification. Consensus
statements and clinical practice guidelines framed by 1. Hyman SL, Levy SE, Myers SM. AAP Council on Children

with Disabilities, Section on Developmental and 2015;52:141-3.

Behavioural Pediatrics. Identification, Evaluation, and 6. Hodges H, Fealko C, Soares N. Autism spectrum disorder:
Management of Children with Autism Spectrum Disorder. Definition, epidemiology, causes, and clinical evaluation.
Pediatrics. 2020;145:e20193447. TranslPediatr. 2020;9(Suppl 1):S55-S65.
2. Johnson CP, Myers SM, and the Council on Children with 7. Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation
Disabilities. Identification and Evaluation of Children with in identifying the etiology of autism spectrum disorders:
Autism Spectrum Disorders. Pediatrics. 2007;120:1183- 2013 guideline revisions. Genet Med. 2013:15:399-407.
215. 8. AAP Medical Home Initiatives for Children with Special
3. Myers SM, Johnson CP, and the Council on Children with Needs Project Advisory Committee. The Medical Home.
Disabilities. Management of Children with Autism Pediatrics. 2002;110:184-6.
Spectrum Disorders. Pediatrics. 2007;120:1162-82. 9. Dalwai S, Ahmed S, Udani V, Mundkur N, Kamath SS,
4. American Psychiatry Association. Diagnostic and Nair MKC. Consensus Statement of the Indian Academy of
Statistical Manual of Mental Disorders, 5th ed. Arlington, Pediatrics on Evaluation and Management of Autism
VA: American Psychiatric Publishers; 2013. Spectrum Disorder. Indian Pediatr. 2017;54:385-93.
5. Sharma N, Mishra R, Mishra D. The fifth edition of 10. Subramanyam AA, Mukherjee A, Dave M, Chavda K.
diagnostic and statistical manual of mental disorders Clinical Practice Guidelines for Autism Spectrum
(DSM-5): What is new for the pediatrician? Indian Pediatr. Disorders. Indian J Psychiatry. 2019;61:254-69.

RESEARCH LETTERS
Six (15%) patients required intensive care. Of the study

A Preliminary Report of COVID-19 population, only 63.4% had a positive contact history. One
in Children in India child died in this series due to type II respiratory failure with
septic shock in a case of post adenoviral bronchiolitis obliterans
and hypoxic brain injury.
We describe the profile of COVID-19 in children from India in this
multicentre observational study from tertiary care hospitals in Our study found that the clinical course of COVID-19 in
West Bengal. Data of children up to 12 years presenting with children appeared to be less severe than that reported in adults,
positive results on SARS-CoV-2 RT-PCR test were included. The which is consistent with other reports published on COVID-19
median (IQR) age of the 41 patients included was 1 (0.42-5.0) in children. We also found that co-morbidities were more
year. Eleven (26.8%) patients, including 6 neonates, never
prevalent (61%) in the 41 children hospitalized with COVID-
showed any symptoms. Fever was seen in only 9 patients (21%),
and co-morbities were found in 61% of patients. There was one 19 [2]. Comorbidities among children with COVID-19 were
death. reported in all patients from China [3] but in 83% of those in US
and Canadian intensive care units [4].
Keywords: Co-morbidities, Course, Management, Outcome.
Some studies [5] have raised concerns about the
appearance of a novel severe Kawasaki-like disease in children
T
he clinical profile of Corona Virus Disease 2019
in association with SARS-CoV-2 infection [6]. Our study also
(COVID-19) infection in children is variable, and
information from developing countries is not readily
available, except for China [1]. We report a series of Table I Characteristics of Children With COVID-19 (N=41)
pediatric cases of COVID-19 from eastern India.
Characteristics No. (%)
We collected data of children younger than 12 years
admitted in tertiary care institutes, including COVID Age group
designated hospitals, of West Bengal. The children were <28 d 6 (14.6)
included after obtaining parental consent, if they had a positive 28 d -<1 y 12 (29.3)
RT-PCR test report for SARS-CoV-2. The study was conducted
1-5 y 15 (36.6)
from March, 2020 to June, 2020. Ethical permission was sought
from the institutional ethics committee. 6-10 y 6 (14.6)
>10 y 2 (4.9)
RT-PCR for SARS-CoV-2 in an Indian Council of Medical
Symptoms*
Research (ICMR) approved medical laboratory, data regarding
clinical details, exposure history, hospital course and outcome Asymptomatic 11(26.8)
were collected in pre-designed proforma. The records were Mildly symptomatic 14 (34.1)
entered and updated by pediatric residents and subsequently Respiratory distress 13 (31.7)
reviewed by a senior pediatric faculty of the institute. Data were Fever 9 (21.0)
compiled in Microsoft Excel spreadsheet and summarized. Cough 5 (12.1)
We studied 41 patients (24 boys) with the median (IQR) age Diarrhea 3 (7.3)
of 1 (0.42-5.0) year. Majority of the cases, 40 (97.6%) were Rashes 2 (4.9)
successfully discharged, with one death. We had 6 neonates Co-morbidity 25 (60.9)
with COVID-19, all of whom were born to SARS-COV-2
Malignancy 8 (19.5)
positive mothers and were asymptomatic. Of the rest, five
patients never showed any symptoms throughout the period of Hematological disorders 5 (2.2)
isolation, while 14 (34%) were mildly symptomatic in the form Congenital heart disease 4 (9.7)
of common cold and rhinorrhea. Fever, which is perceived to be Neurological abnormalities 4 (9.7)
a major presenting feature of COVID-19, was seen only in 9 Chronic lung disease 2 (4.9)
patients (21%).
Multiple congenital anomalies 2 (4.9)
Two cases had multi-system involvement in the form of an Respiratory support
atypical Kawasaki disease-like presentation. Almost 61% of the Oxygen 10 (24.4)
cases had associated co-morbidities (Table I). Eleven (26.8%)
High flow nasal cannula 2 (4.9)
patients needed no active management, 34% mildly
symptomatic children needed nasal drops and anti-histaminics, Ventilation 2 (4.9)
24.4% required oxygen inhalation, 4.9% were put on high flow *Shock, convulsions and sepsis like illness were present in one child
nasal canula (HFNC) and 4.9% needed mechanical ventilation. each.

RESEARCH LETTERS
had two such cases with multi-system involvement in the form children with 2019 novel coronavirus infection: Clinical and
of an atypical Kawasaki - like presentation, similar to previous epidemiological features. Clin Infect Dis. 2020:ciaa198.
Indian reports [7]. [Epub Ahead of print 2020 Fen 28]
2. Garg S, Kim L, Whitaker M, Halloran A, Cummings C,
In a recent meta-analysis, Meena, et al. [8] analyzed data
Holstein R, et al; US Centers for disease control and
from 27 different studies (4857 patients). They showed that
prevention. Hospitalization rates and characteristics of
even among the symptomatic COVID-19 cases, severe
patients hospitalized with laboratory-confirmed coronavirus
manifestations are fewer in children. They found that fever and
disease 2019—COVID-NET, 14 states, March 1-30, 2020.
respiratory symptoms are most common, although many
Available from: https://www.cdc.gov/mmwr/volumes/69/wr/
children had gastrointestinal manifestations [8].
mm6915e3.htm. Accessed June 30, 2020.
The study has its share of limitations of small sample size 3. Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ,
and lack of long term follow up of co-morbidities after Ross CE, McKiernan CA, et al. Characteristics and outcomes
discharge. In spite of these shortcomings, this study provides of children with coronavirus disease 2019 (COVID-19)
preliminary data on characteristics and outcomes of COVID-19 infection admitted to US and Canadian pediatric intensive
in children from India. care units. JAMA Pediatr. 2020;10 [published online ahead
Contributors: SB: primary investigator, data collection, making of print, 2020 May 11]
draft; AG: making draft, literature search, interpretation, 4. Lu X, Zhang L, Du H. SARS-CoV-2 infection in children. N
statistical help; AD: data collection, draft, Literature search; MN: Engl J Med. 2020;23;382;17.
technical inputs, data collection, study conception, review draft; 5. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M,
RM: conception of study, reviewing draft, Study design, and Ciuffreda M, et al. An outbreak of severe Kawasaki-like
literature search. All authors approved the final manuscript. disease at the Italian epicentre of the SARS-CoV-2 epidemic:
Funding: None; Competing interest: None stated. an observational cohort study. Lancet. 2020. Available from
Published online: July 28, 2020; PII: S097475591600217 https://doi.org/10.1016/S0140-6736(20) 31103-X. Accessed
June 30, 2020.
SOURAV BANERJEE,1 ARITRA GUHA,2 AVISHIKTA DAS,2 6. Viner RM, Whittaker E. Kawasaki-like disease: Emerging
MOUSAMI NANDI1 AND RAKESH MONDAL1* complication during the COVID-19 pandemic. Lancet.
Departments of Pediatrics, 2020;395:1741-3.
1Medical College Kolkata, Kolkata;
7. Acharyya BC, Acharyya S, Das D. Novel coronavirus,
and 2NB Medical College, mimicking Kawasaki disease in an infant. Indian Pediatr.
Darjeeling; West Bengal, India. 2020;S097475591600184 [E-pub ahead of print].
*ivanrakesh2001@gmail.com
8. Meena J, Yadav J, Saini L, Yadav A, Kumar J. Clinical
REFERENCES features and outcome of SARS-CoV-2 infection in children:
A systematic review and meta-analysis. Indian Pediatr.
1. Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, et al. A case series of 2020;S097475591600203 [E-pub ahead of print].
disturbances occurring in the fetal or infant brain [1]. Since

Effect of Robot-Assisted Gait robot-assisted gait training (RAGT) induces changes in the
Training on Selective Voluntary brain plasticity, it appears promising in improving gross motor
control of CP children with cerebral palsy [2-4].It could be
Motor Control in Ambulatory hypothesized that RAGT can affect impaired selective
voluntary motor control (SVMC), which is the inability to
Children with Cerebral Palsy activate muscles to achieve a voluntary posture or movement
[5]. Therefore, this pilot study investigated the efficacy of
This pilot study investigated the efficacy of a four week robot- RAGT as monotherapy on lower limb SVMC, joint range of
assisted gait training in twelve children with spastic diparesis. motion (ROM), walking ability, and gross motor measures.
Short-term results and a 3-month follow-up showed statistically
significantly increased selective motor control, walking farther The study received ethics committee approval from
distances, gross motor score, and decreased joint contractures. participating institutions. All parents and children provided
Keywords: Cerebral palsy, Gait, Joint range of motion, Lokomat, written informed consent for participation. Twelve children
Motor control, [mean (SD) age, 10.9 (3.3) year; 2 girls] were tested at the
baseline, after four weeks of intervention, and at 3-month
follow-up. Children with spastic diparesis with toe-walking
and/or scissoring patterns aged between 5-17 years were
Cerebral palsy affects movement and posture, resulting in a recruited. Only children who could attend the 4-week RAGT
limited activity that is attributed to non-progressive program regularly were enrolled. Children were excluded if

RESEARCH LETTERS
they had used any muscle relaxants within the previous 6 improves SVMC and decreases hip joint internal rotation
months or had orthopedic surgery within the last year [2-4]. contractures. We support the previous results that CP children
increased walking distance following RAGT [2-4]. It has been
Standardized, validated questionnaires and evaluations [5-8] shown that the combination of RAGT and physiotherapy
were used: goniometry, Selective Control Assessment of Lower improves GMFM D,E scores [2-4].
Limbs Evaluation (SCALE), D and E parts of Gross Motor
Function Measurement (GMFM), 10-meter walk test (10MWT) Our outcomes suggest that although expensive (~300,000
and 6-minute walk test (6MWT). During walking tests, all Euro), RAGT, which is primarily used in rehabilitation centers,
children wore footwear and orthoses, if regularly used. For can improve D, E scores even when used as a stand-alone
SCALE, children performed isolated movements of the hip, knee, therapy. Although this study provides a foundation on which
ankle, subtalar, and toe joints. Scores were assigned as: normal - future studies can be built on, RAGT should be investigated
joints moved selectively within at least 50% of the possible ROM, over longer periods in different populations to further
and at a physiological cadence; impaired - movement performed determine its effectiveness.
slower below 50% of ROM, with mirror and/or synergistic
Ethical Approval: (i) Charles University, Prague, the
movements; or unable - no joint movement performed or synergy
Czech Republic (number 120/2015) dated August 12, 2015, and
patterns present. Pre-post intervention goniometry and SCALE
(ii) University Rehabilitation Institute, Ljubljana, the Republic
evaluations showed bilateral asymmetries in lower limbs across
of Slovenia on October 5, 2015.
all children. Asymmetries were recorded as ‘more impaired limb
Contributors: DZ: conducted the research, drafted the work,
(MIL)’ and ‘less impaired limb (LIL)’.
revising and writing final approval of the version to be
The Lokomat Pro device (Hocoma AG, Volketswil, published; DZ, JJT, MS, PK, SV, KG-S, DR: substantial contri-
Switzerland) was used [9]. Children attended 20 sessions butions to the conception or design of the work; the acquisition,
scheduled on 20 consecutive working days. Therapy ranged 30- analysis, and interpretation of data for the work; revising the
45 minutes and progressively increased by at least 3 minutes work critically for important intellectual content; final approval
every other day [mean (SD), 39 (6) minute]. Walking speed of the version to be published; agreement with all co-authors to
[mean (SD), 1.4 (2.38) km/h] was set individually. The walking be accountable for all aspects of the work in ensuring that
distance [mean (SD), 969 (172) meter] was gradually increased questions related to the accuracy or integrity of any part of the
every other day by at least 50 meters. All children had an initial work are appropriately investigated and resolved.
level of 50% body-weight support [mean (SD), 14.8 (4.76) kg], Funding: Supported by a grant entitled ‘Project FTVS SVV
which was gradually decreased every other day for each child 2017-2019-260346’ from Charles University in Prague, Czech
until the knee did not start to collapse into flexion during the Republic. This study was written within the program of the
stance phase. institutional support for science at Charles University Progress,
No. Q41, Biological aspects of the investigation of human
Data were analyzed in MatLab (Mathworks Inc., USA). movement. Slovenian Research Agency (research core funding
Shapiro-Wilk test (0.05 significance level) showed abnormal P2-0228);
data distribution. The Wilcoxon sign rank test was used for the Competing interests: None stated.
LIL and MIL, separately [10]. Spearman correlations were
calculated for the following: goniometry/SCALE, GMFM D, E/ DRAGANA ZARKOVIC,1* MONIKA SORFOVA,1
10MWT, and GMFM D, E/6MWT. JAMES J TUFANO,2 PATRIK KUTILEK,3 SLAVKA VITECKOVA,3
KATJA GROLEGER-SRSEN4 AND DAVID RAVNIK5
Hip joint flexion contractures decreased bilaterally by 10° Departments of 1Anatomy and Biomechanics,
(P=0.004). Internal hip rotations decreased by 10° in LIL and 2Physiology and Biochemistry, Faculty of Physical Education
15° in MIL (P=0.002). Ankle dorsiflexion improved bilaterally and Sport, José Martího, Prague, the Czech Republic;
by 10° (P=0.001). SCALE scores increased by 1.5 in LIL and 3Department of Natural Sciencces, Faculty of Biomedical
2.5 points in MIL (P=0.001). The 6MWT walking distance Engineering, nam. Sitna, Kladno, the Czech Republic;
increased by 75 meters (P=0.001). 10MWT showed no 4Children’s Rehabilitation Department, Faculty of Medicine,
significant change (P=0.89). GMFM-D improved by 8% University of Ljubljana, University Rehabilitation Institute,
(P<0.001) and GMFM-E by 6% (P=0.002). Correlations were Linhartova cesta, Ljubljana and 5Department of Nursing Care,
found only between GMFM D, E scores and walking tests Faculty of Health Sciences, University of Primorska, Polje,
(rho=-0.614-0.784;P<0.05). Increased GMFM scores corre- Izola, Republic of Slovenia.
lated with decreased time in 10MWT, and increased walking *dragana.z@seznam.cz
distance in 6MWT. There was no significant difference in short-
term and 3-month follow-up data (P>0.05) across all measures. REFERENCES
Since active training seems to be more effective than 1. Jeevanantham D. Application of the international
passive training for motor learning and cortical reorganization classification of functioning, disability and health -
in central motor impairments [2-4,9], RAGT likely improved children and youth in children with cerebral palsy. Indian
motor control of CP children due to active training performed Pediatr. 2016; 53:805-10.
with a high-repetition-rate of guided movements in the most 2. Borggraeffe I, Schemer JS, Klaiber M, Dabrowski E,
neutral pelvis and lower limbs position. To the best of our Ammann-Reiffer C, Knecht B, et al. Robotic-assisted
knowledge, this is the first study suggesting that RAGT treadmill therapy improves walking and standing

RESEARCH LETTERS
performance in children and adolescents with cerebral Dev Med Child Neurol. 2009;51:607-14.
palsy. Eur J Paediatr Neurol. 2010;14:496-502. 6. Janda V, Pavlu D. Goniometrie. Brno: Institut pro dalsi
3. Hilderley AJ, Fehlings D, Lee GW, Wright FV. vzdelavani pracovniku ve zdravotnictvi; 1993.
Comparison of a robotic-assisted gait training program 7. Alotaibi M, Long T, Kennedy E, Bavishi S. The efficacy of
with a program of functional gait training for children with GMFM-88 and GMFM-66 to detect changes in gross motor
cerebral palsy: design and methods of a two group function in children with cerebral palsy (CP): A literature
randomized controlled cross-over trial. Springer Plus. review. Disabil Rehabil. 2014;36:617-27.
2016;5:1886. 8. Thompson P, Beath T, Bell J. Test-retest reliability of the
4. Vrecar I, Majdic N, Jemec I, Damjan H. Changes in passive 10-metre fast walk test and 6-minute walk test in
range of motion of joints of the lower limbs in children with ambulatory school-aged children with cerebral palsy. Dev
cerebral palsy after an intense training program on the Med Child Neurol. 2008;50:370-6.
Lokomat. Rehabilitacija. 2013;12:38-45. 9. Columbo G, Joerg M, Schreier R, Dietz V. Treadmill
5. Fowler EG, Staudt LA, Greenberg MB, Oppenheim WL. training of paraplegic patients using a robotic orthosis. J
Selective Control Assessment of the Lower Extremity Rehabil Res Dev. 2000;37:693-700.
(SCALE): Development, validation, and interrater 10. Cohen J. Statistical Power Analysis for the Behavioral
reliability of a clinical tool for patients with cerebral palsy. Sciences, 2nd edition, New York, 1988.
reviewed the case records of all the patients and extracted

Pediatric Papilledema at a Tertiary information on age and symptoms at presentation, best
Care Ophthalmological Center corrected visual acuity, pupillary response, extraocular
movements, diplopia, fundus biomicroscopy and optic disc
findings at presentation. Body mass index was calculated for all
the patients. Pre pubertal age was considered to be less than 11
Pediatric papilledema is usually asymptomatic and is diagnosed years and pubertal between 11 and 15 years. Best corrected
on routine screening. We conducted a retrospective study to visual acuity was measured using Snellen optotypes and visual
evaluate pediatric papilledema with respect to presentation, field was tested using Bjerrums kinetic perimetry. Neuro-
etiology and treatment at the neuroophthalmology clinic of a imaging of brain (magnetic resonance imaging (MRI) or MR
tertiary care eye institute.19 of the 24 children studied had venogram) findings and serological evaluation including
Idiopathic intracranial hypertension.This study stresses upon the
complete hemogram, thyroid function tests were recorded.
interdisciplinary approach for prompt diagnosis and treatment of
papilledema. Results of lumbar puncture and cerebrospinal fluid analysis
were available for only one patient, due to lack of consent in
Keywords: Diagnosis, Idiopathic intracranial hypertension,
others.
Management, Referral.
Twenty-four patients met the inclusion criteria and the
mean age was 11.3 years, youngest was a 2-year-old child. Girls
were more frequently affected (13, 54.1%). The commonest
Papilledema is defined as optic disc edema secondary to high
presenting symptom was headache (n=12), followed by double
intracranial pressure, the etiology for which may be known or
vision (n=7), and defective vision (n=6). Few patients
unknown (idiopathic) [1]. Idiopathic intracranial hypertension
presented with sudden onset of ocular deviation (n=2), pain on
(IIH) is typically defined by exclusion using modified Dandy
eye movement (n=2), radiating neck pain (n=2) and frequent
criteria [2]. IIH typically affects obese women of childbearing
blinking (n=1). Best corrected visual acuity remained 20/20 in
age, but it may be seen in patients of any age or weight [3].
18 of our patients in both eyes, while 6 (25%) patients presented
Obesity and weight gain appear to be risk factors during
with visual morbidity. Of those, three had IIH and others were
adolescence but not in pre pubertal age group [4]. Pediatric IIH
due to secondary causes. Pupillary examination and color
is diagnosed in many asymptomatic children during a routine
vision remained normal in all our patients except in one
encounter [5].
diagnosed with craniopharyngioma. Sixth nerve palsy was seen
Pediatric central nervous system tumors are the second in 12.5% (n=3) of patients,and 87.5% (n=21) patients had
most common childhood malignancies, and hence is a major enlarged blind spot on visual field assessment. Overall, 23
etiology of pediatric papilledema. The purpose of this study was (96%) patients had bilateral disc edema and one had unilateral
to evaluate papilledema in the pediatric age group at the neuro- disc edema on fundus examination. The most common etiology
ophthalmology clinic of a tertiary eye care center. in our population was found to be IIH in 79% (n=19),
intracranial tumors in 12.5%, and the rest falling under infective
A review of hospital records of papilledema patients in the etiology and obstructive hydrocephalus (TableI).
pediatric age group (<15 years) was done for the period January,
2016 – December, 2018. Patients with pseudo papilledema and IIH in children and adolescents is relatively uncommon and
those on previous treatment were excluded from the study. We may be associated with puberty and resulting hormonal changes

RESEARCH LETTERS
[6]. In pre-pubertal children, IIH appears to be even less diagnosis and proper management can prevent needless
frequent;we found three girls and three boys each in the pre- blindness resulting from secondary optic atrophy and also play
pubertal age. Children with IIH are reported to have an equal a significant role in saving the life of children. This study
sex distribution [7], though we found a male female ratio of 1:2. emphasizes that ophthalmologists play a key role in monitoring
Affected adolescents of IIH tend to be overweight, but obesity for visual morbidity following papilledema and also stresses
and weight gain do not appear to be risk factors [8]. In our series upon the interdisciplinary approach for prompt diagnosis and
one girl was obese, two were overweight; one of whom was in treatment of papilledema.
pubertal age. Acute headache and double vision were the
Funding:None; Competing interests: None stated.
common symptoms on initial presentation and none of our
patients were picked upon routine examination. We had three MURUGESAN MAHESWARAN,1 MULASTHANAM SAI DHEERA,2
patients with sixth nerve palsy as false localizing sign, who MAHESH KUMAR3 AND AKKAYASAMY KOWSALYA3*
presented with sudden squinting. Departments of 1,2Opthalmology and 3Neuro-ophthalmology,
Aravind Eye Hospital and Post Graduate Institute of
Visual loss has been reported to occur in children with IIH.
Ophthalmology, Madurai, Tamil Nadu, India.
Pediatric IIH is just as threatening to vision as the adult form *kowsalyabalaji@gmail.com
[6], in our study we encountered visual morbidity in three of our
REFERENCES
patients. Enlarged blind spot, which has been reported to occur
in virtually all eyes with papilledema,was found in our patients 1. Lee AG, Wall M. Papilledema: are we any nearer to a
also. Accurate visual field testing in children is sometimes consensus on pathogenesis and treatment? Curr Neurol
difficult to perform, and hence difficult to rely on as the only Neurosci Rep. 2012;12:334-9.
accurate test. We suggest performing a kinetic perimetry in 2. Friedman DI, Jacobson DM. Diagnostic criteria for
young and uncooperative children. Symmetric papilledema was idiopathicintracranial hypertension. Neurology. 2002;59:
recorded in eighteen children and one boy had unilateral 1492-95.
papilledema.In this series, all our patients were referred to 3. Dhungana S, Sharrack B, Woodroofe N. Idiopathic
neurophysician and medically managed with oral intracranial hypertension. ActaNeurol Scand. 2010;121:
acetozolamide and responded well to treatment. None of our 71-82.
patients needed Optic nerve sheath decompression. 4. Aylward SC, Reem RE. Pediatric intracranial hyper-
tension. Pediatr Neurol. 2017;66:32-43.
Brain tumors with the greatest direct threat to the visual
5. Bassan H, Berkner L, Stolovitch C. Asymptomatic
pathways are tumors that involve the optic pathway, parasellar
idiopathic intracranial hypertension in children. Acta
tumors, and cerebral hemispheric tumors [8].We had one
Neurol Scand. 2008;118:251-5.
patient with pilocytic astrocytoma, the commonest cerebral
6. Lessell S. Pediatric pseudotumorcerebri (idiopathic
hemispheric lesion which causes vision loss due to secondary
intracranial hypertension).SurvOphthalmol. 1992;37:155-
optic atrophy following papilledema. Craniopharyngioma, the
66.
most common supratentorial tumor of childhood exhibits a
7. Babikian P, Corbett J, Bell W. Idiopathic intracranial
bimodal age distribution. In our series, it was diagnosed in a 15-
hypertension inchildren: The Iowa experience. J Child
year-old boy with chronic visual deficit in one eye with
Neurol. 1994;9:144-9.
papilledema [9].Though tuberculosis is common in India,
8. Edmond JC. Pediatric brain tumors: The neuro-ophthalmic
tuberculous brain abscess is rare [10].Our patient with multiple
impact. Int OphthalmolClin. 2012;52:95-106.
tubercular cerebral abscess and midline shift had papilledema
9. Merchant TE, Pollack IF, Loeffler JS. Brain tumors across
as the primary manifestation and was treated with anti-
the age spectrum: Biology,therapy, and late effects.
tuberculous therapy and recovered completely.
SeminRadiatOncol. 2010;20:58-66.
In summary, IIH is a common cause of papilledema in 10. Andronikou S, Greyling PJ. Devastating yet treatable
Indian children, and they are mostly symptomatic during complication of tuberculous meningitis: The resistant TB
presentation and respond well to medical management. Prompt abscess. ChildsNervSyst.2009;25:1105-06.
Noonan syndrome is a genetic disorder with an estimated

Noonan Syndrome in Thai prevalence of 1 in 1,000 to 2,500 live births [1]. The typical
Children facial features include ptosis, widely spaced eyes, down slanted
palpebral fissures, and low set ears [2]. Early and accurate
diagnosis of NS is essential as each patient needs an individual
This study describes clinical features of Noonan syndrome and treatment regimen, and has distinct recurrent risk and prognosis
gene mutations, including PTPN11, SOS1, and BRAF in the Thai
[3]. Due to limited resources for genetic testing for the disorder,
population.Widely spaced eyes were the most common finding
from the digital facial analysis technology used in this study. facial analysis technology may be useful to identify new cases.
The digital facial analysis technology has previously been used
Keywords: Facial analysis technology, Gene mutation, PTPN11.
to identify individuals with Noonan syndrome from 20

RESEARCH LETTERS
countries. The sensitivity and specificity of the test for Noonan Acknowledgments: Antonio R. Porras and Professor Marius
syndrome in the Asian population was reported to be 0.95 and George Linguraru, Sheikh Zayed Institute for Pediatric Surgical
0.90, respectively [5]. This study reports common physical Innovation, Children’s National Hospital, Washington DC for
findings with the facial analysis technology evaluation and facial profile data analysis. Dr. Paul Kruszka, Medical Genetics
genetic testing in children with Noonan syndrome in Thailand. Branch, National Human Genome Research Institute, NIH, for
genetic testing.
Participants were enrolled at Chiang Mai University
Ethics approval: Ethics Research Committee of the Faculty of
Hospital including patients with clinical features of Noonan
Medicine, Chiang Mai University; No. PED-2559-04024 dated
syndrome, and those without these features as controls.
9 September, 2016.
Informed consent was obtained from all participants. Medical
Contributors: All authors contributed to the study design, data
records were also reviewed, and photographs of patients were
interpretation, drafting the article/critical review and final
sent to the Children’s National Hospital for analysis via secure
approval of the manuscript.
encrypted email.
Participants were 12 children (4 females) with
clinical features of Noonan syndrome. The mean (SD) age was NONGLAK BOONCHOODUANG,1*ORAWAN LOUTHRENOO1 AND
5.19 (4.53) year (range 3 month – 17 year). Nine children were PRANOOT TANPAIBOON2
1Department of Pediatrics, Faculty of Medicine,
further evaluated by the digital facial analysis technology (Case
No.1-9) and 7 cases (Case No.1-4 and 10-12) were identified by Chiang Mai University, Chiang Mai, Thailand; and
2Division of Genetics and Metabolism,
gene sequencing. The details of 12 individuals are shown in
Web Table I. Children National Health System,
Washington, District of Columbia, USA.
Hypertrophic cardiomyopathy (HCM) was the most *nonglak.b@cmu.ac.th
common cardiac defect found in this study, followed by
pulmonary valve stenosis (PVS) and atrial septal defect (ASD). REFERENCES
Novel gene mutations were found in 57.1% cases with gene 1. Mendez HM, Opitz JM. Noonan syndrome: A review. Am
sequencing identification. Three genes that carried mutations J Med Genet. 1985;21:493-506.
were PTPN11 (71.4%), SOS1 (14.3%) and BRAF (14.3%). 2. Allanson JE, Hall JG, Hughes HE, Preus M, Witt RD.
The most common phenotype from the digital facial Noonan syndrome: The changing phenotype. Am J Med
analysis technology in this study is widely spaced eyes, which is Genet. 1985;21:507-14.
consistent with a previous study [5]. Significant different 3. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B,
texture features of Thai patients with normal controls were the Pierpont ME, et al. Noonan syndrome: Clinical features,
texture at upper eyelid (P=0.004), nose apex (P<0.001), cupid’s diagnosis, and management guidelines. Pediatrics. 2010;
bow (P=0.005), oral commissure (P<0.001), center of ala of the 126:746-59.
nose (P=0.003), and nostril (P<0.001). 4. Zhao Q, Okada K, Rosenbaum K, Kehoe L, Zand DJ, Sze
R, et al. Digital facial dysmorphology for genetic
The frequency of cardiac defect is different from a previous screening: Hierarchical constrained local model using ICA.
report from China [6], which found ASD as the most common Med Image Anal. 2014;18:699-710.
defect (50%), followed by PVS (20%). Isojima, et al. [7] found 5. Kruszka P, Porras AR, Addissie YA, Moresco A, Medrano
that PVS was the most common cardiac defect in Japanese S, Mok GTK, et al. Noonan syndrome in diverse
patients (52.6%), followed by HCM (27.3%) and ASD (21.4%) populations. Am J Med Genet A. 2017;173:2323-34.
[7]. Despite these variations, the three common defects in 6. Xu S, Fan Y, Sun Y, Wang L, Gu X, Yu Y. Targeted/exome
Noonan syndrome are HCM, PVS, and ASD [8]. sequencing identified mutations in ten Chinese patients
Most patients had PTPN11 gene mutation, similar to the diagnosed with Noonan syndrome and related disorders.
study by Tartaglia, et al. [9]. De novo mutations account for BMC Med Genomics. 2017;10:62.
57.1% of cases, consistent with a previous study, which found 7. Isojima T, Sakazume S, Hasegawa T, Ogata T, Nakanishi T,
60% of cases with novel mutations [10]. Nagai T, et al. Growth references for Japanese individuals
with Noonan syndrome. Pediatr Res. 2016;79:543-8.
As identification was done by clinical features, only severe
8. Pierpont ME, Digilio MC. Cardiovascular disease in
phenotypes were included in the evaluation by the facial
Noonan syndrome. Curr Opin Pediatr. 2018;30:601-8.
analysis technology or gene testing. Lastly, complete genetic
9. Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van
testing for all cases with the facial analysis technology would
der Burgt I, et al. PTPN11 mutations in Noonan syndrome:
provide more information adding to the clinical features.
Molecular spectrum, genotype-phenotype correlation, and
This study describes clinical features of Noonan syndrome phenotypic heterogeneity. Am J Hum Genet. 2002;70:
and gene mutations in the Thai population. The feature of 1555-63.
widely spaced eyes was the most common facial appearance 10. Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA.
found by digital facial analysis technology. This may be a The natural history of Noonan syndrome: A long-term
helpful clue in suspecting Noonan syndrome by clinicians. follow-up study. Arch Dis Child. 2007;92:128-32.

CLINICAL CASE LETTER
By the third day, the child’s sensorium had significantly

COVID-19 in a Child With Diabetic improved and glycemic control had been achieved and she was
Ketoacidosis: An Instigator, a weaned to high flow nasal cannula. However, during the course
of the day she developed tachycardia, decreased urine output
Deviator or a Spectator and sudden onset hypotension requiring two normal saline
boluses of 20mL per kg to restore her circulatory status.
Following the fluid resuscitation, there was worsening of the
base line tachypnea without the requirement of supplemental
oxygen. A rise in creatinine to a maximum of 2 mg/dL from a
W
e report severe acute respiratory syndrome
baseline of 0.4 mg/dL was also documented which took two
coronavirus 2 (SARS-CoV-2) precipitated
days to normalize despite optimal fluid status maintained by
diabetic ketoacidosis in a child with newly
intravenous fluids and nasogastric tube feeds. Despite good
diagnosed type 1 diabetes mellitus with mild
control of blood sugars and resolution of ketonuria, the child
hyperinflammatory syndrome leading to fluid responsive shock.
was noticed to have persistent severe metabolic acidosis and
A 15-year-old previously asymptomatic girl presented to hyperchloremia which gradually improved over the next four
the emergency department in the first week of May, 2020, with days. By day 5, acidosis and appetite improved, hence she was
complaints of acute onset of abdominal pain and vomiting. At switched over to 3-hourly subcutaneous insulin according to a
the referring hospital, she was noted to have hyperglycemia and sliding scale for the first day followed by basal bolus regimen
severe metabolic acidosis (pH 6.9, bicarbonate 2 mEq/L). She and was discharged after 14 days of hospital stay.
was initiated on a fluid bolus and was referred to our center.
There have been many reports on new onset diabetes in
On admission to the pediatric intensive care unit, the child SARS-CoV-2 positive patients as well as worsening of glycemic
was observed to be lethargic (GCS-14). On clinical examination, control in those with preexisting diabetes mellitus [1]. However,
she had normal blood pressure with heart rate of 140/minute, majority of the world wide data point towards type 2 diabetes,
cold extremities, tachypnea (respiratory rate 40/minute) and with only a few anecdotal reports of COVID-19 infection in
Kussmaul breathing. She had short stature (with a height of 145 individuals with juvenile diabetes [2]. The expression of
cm, <-2 SD) normal body mass index (19 kg/m2), and nofeatures angiotensin converting enzyme 2 (ACE-2) receptors on
of insulin resistance. Systemic examination was unremarkable pancreatic β cells can lead to direct injury to pancreatic beta cells
except for mild generalized abdominal tenderness. Her blood and decreased insulin secretion which might then precipitate
investigations revealed random blood sugar of 414 mg/dL, ketoacidosis [3].Similar cases have been reported in the viremic
neutrophilic leukocytosis, and serum potassium was 2 mEq/L. phase of other viral illnesses like H1N1 too [4].
Her urine showed 4+ ketones, and arterial blood gases were
suggestive of severe compensated metabolic acidosis Multiple questions regarding the association of COVID-19
(pH=7.03). Her HbA1C was 13.5%. and diabetic ketoacidosis remain unanswered such as
precipitation in a child with previously undiagnosed diabetes
Fluid deficit replacement followed by insulin infusion at (suggested by a highly elevated HbA1c level); the cause of
0.1unit/kg/hour was initiated. Over the next 6 hours, the blood circulatory collapse despite adequate initial fluid resuscitation,
sugars began normalizing at a rate of around 50 mg/dL per hour; and the mechanism of renal injury (prerenal) seen in the child.
however, severe metabolic acidosis persisted. This was Although GAD antibodies were negative, absence of obesity,
accompanied with a clinical deterioration of sensorium and markers of insulin resistance and negative family history
onset of shallow breathing pattern with a rapid rise in partial favored the clinical diagnosis of type 1 diabetes.
pressure of carbon dioxide (pCO2) and oxygen desaturation on
arterial blood gas, requiring the initiation of non-invasive The COVID infection most probably also triggered the
ventilation. A chest radiograph at the time revealed low volume hyperinflammatory response in the child leading to third
lung with mild bilateral haziness. In view of the possibility of spacing and the fluid responsive shock with subsequent early
cerebral edema, 3 mL/kg of 3% sodium chloride was infused over acute tubular necrosis and mild acute kidney injury [5]. The
20 minutes, and fluid intake was optimized. With these circulatory collapse was observed to occur in the first 4-5 days
measures, sensorium, pCO2 and oxygen saturation improved. of illness in the patient which probably coincides with the peak
The nasopharyngeal swab reverse transcriptase polymerase of viremia. The increased work of breathing during the fluid
chain reaction, done as per institutional protocol for all resuscitation also points towards the need of slower and
inpatients, was positive for SARS-CoV-2. Oral hydroxy- judicious fluid resuscitation in diabetic ketoacidosis or shock,
chloroquine (6.5 mg/kg twice daily for 1 day followed by 3.25 especially in the setting of COVID- related pulmonary capillary
mg/kg twice daily for 4 days) was added to the treatment leak. Lastly, the hyperchloremic metabolic acidosis took more
regimen. She had a low grade fever on the second day of than 96 hours to get corrected in spite of tailoring the chloride
admission, which was managed symptomatically. content of iv fluid which is an unusual and atypical pattern. The

CLINICAL CASE LETTERS
above clinical presentation may fit into a pediatric inflammatory 2020;164:108166.

multisystem syndrome (PIMS) associated with COVID-19 2. Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins
[6]. However, further data is required to shed light on the D, Birkenfeld AL, et al. Practical recommendations for the
complex and varying presentations of coronavirus infection in management of diabetes in patients with COVID-19.
children with and without associated co-morbidities. Lancet Diab Endocrinol. 2020;8:546-50.
3. Yang J, Lin S, Ji X, Guo LM. Binding of SARS coronavirus
Published online: July 15, 2020; PII: S097475591600211.
to its receptor damages islets and causes acute diabetes.
SANILA DANIEL,1* BHUSHIT GADHIYA,1 AKANKSHA Acta Diabetol. 2010;47:193-99.
PARIKH2 AND PREETHA JOSHI1 4. Tan H, Wang C,Yu Y. H1N1 influenza: The trigger of
Departments of Pediatric Intensive Care and 2Pediatrics,
1 diabetic ketoacidosis in a young woman with ketosis-prone
Kokilaben Dhirubhai Ambani Hospital diabetes. Am J Med Sci. 2012;343:180-83.
and Research Institute, 5. H Su, M Yang, C Wan, Yi LX, Tang F, Zhu HY, et al. Renal
Mumbai, Maharashtra, India. histopathological analysis of 26 postmortem findings of
*drsaniladaniel@gmail.com patients with COVID-19 in China. Kidney Int.
2020;98:219-27.
REFERENCES
6. Royal College of Paediatrics and Child Health. Guidance:
1. Chee YJ, Ng SJH, Yeoh E. Diabetic ketoacidosis Paediatric multisystem inflammatory syndrome tempo-
precipitated by Covid-19 in a patient with newly diagnosed rally associated with COVID-19. UK: Royal College of
diabetes mellitus. Diabetes Res Clin Pract. Paediatrics and Child Health; 2020.
ADVERTISEMENT

CORRESPONDENCE
disinfection of the adaptive devices like wheelchairs, orthotics,

Managing Children with Special hearing aids etc. should be stressed upon.
Needs in COVID-19 Times Parents should try to maintain some schedule for their
children by following online school sessions and engaging them
in fun based household chores. Wherever possible, these
children should be encouraged to continue social interaction
through supervised telephonic and video calls. Avoiding extra
Children with special needs are facing additional predicament demands and unrealistic expectation from children during these
of understanding and dealing with the challenges brought about times may help in eluding frustration and behavioral issues.
by the ongoing pandemic due to their unique health conditions.
As far as possible, clinical focus of specialised treatment
We herein, underscore some of the important issues.
should shift to telehealth services and ‘virtual first’ approach
Challenges: Interruption of requisite therapies can have long- must remain standard practice [5]. Tele-intervention is a viable
term consequences on children with developmental service model for continuing intervention in children with
disabilities. Cessation of regular physiotherapy may worsen disabilities. Apart from questionnaire-based assessments and
functional ability and cause complications like hip dysplasia in guided therapies, it can be helpful for giving psychological
children with cerebral palsy [1]. Lack of a daily schedule can be support to the families and thus reduce chances of abuse and
challenging for children with autism who require reliable neglect.
routines, resulting in irritability and temper tantrums. Lack of
To summarize, during the current pandemic when
understanding of the effects of pandemic, resistance to change
accessibility to essential services is difficult, children with
and inability to adapt to new strategies can lead to pre-existing
disabilities and their parents are a high-risk group for various
behavioral problems intensifying or development of novel
physical and mental health issues, and need appropriate
ones in these children, especially those with autism and
guidance and support.
intellectual disability. Children with attention deficit and
hyperactivity disorder (ADHD) and learning disorder may not Published online: July 24, 2020; PII: S097475591600213.
be able to make effective use of online school sessions due to
MONICA JUNEJA AND ARPITA GUPTA*
poor attention span or difficulty in comprehension [2].
Department of Pediatrics,
Additionally, children with disabilities are at a greater risk of
Maulana Azad Medical College, New Delhi, India.
contracting Covid-19 because of their health-related challenges
*arpita1517@gmail.com
and inability to understand and follow recommended measures
REFERENCES
for infection control [3,4].
1. Ben-pazi H, Beni-adani L, Lamdan R. Accelerating
Parents of these children are also facing tough times. Their
telemedicine for cerebral palsy during the COVID-19
children’s health related stress, which was earlier shared
pandemic and beyond. Front Neurol. 2020;11:1-7.
between parents, schools and therapy centers, has to be dealt
2. UNESCO. Life in the Times of COVID. A Guide for
with by them alone. Perception of delay in child’s progress,
Parents with Special Needs. Available from: https://
inaccessibility to remedial services along with economic
en.unesco.org/sites/default/files/final_parents_guide_
constraints due to lockdown and inability to engage children in
covid_ 19_fn.pdf. Accessed June 29, 2020.
activities throughout the day may impose a huge mental
3. Indian Council of Medical Research. Guidance Document
burden. Thus, mental health counselling for parents is an
for Health System Response for Persons with Disabilities
additional intervention required.
and Functional Impairment During Pandemic i.e. COVID-
Suggestions for care: Since children with special needs may 19. Available from: https://www.scdisabilities.org/resource
not be able to follow the standard respiratory etiquette like /PWD_first%20final.pdf. Accessed June 30, 2020.
wearing of masks and social distancing due to their health 4. WHO Disability considerations during the COVID-19
conditions and behavioral issues, parents can create a circle of outbreak. Available from:https://www.who.int/publications/
protection for their children by stringently following safety i/item/disabilityconsiderations-during-the-covid-19
measures. Visual charts for hand hygiene and social distancing outbreak. Accessed June 5, 2020.
may help children with autism and intellectual disability. For 5. Mahajan V, Singh T, Chandrika V. Using telemedicine
children with visual impairment clear verbal instructions along during the COVID-19 pandemic. Indian Pediatr.
with physical prompts can help [4]. Along with this, 2020;57:652-57.

CORRESPONDENCE
REFERENCES
Diverse Pathophysiology of Sudden
1. Garg D, Sharma S. Sudden unexpected death in epilepsy
Unexpected Death in Epilepsy in (SUDEP) – What pediatricians need to know. Indian
Children Pediatr. 2020;S097475591600192 [published online ahead
of print, 2020 Jun 12].
2. Finsterer J, Wahbi K. CNS disease triggering Takotsubo
stress cardiomyopathy. Int J Cardiol. 2014;177:322-29.
We read with interest the review article by Garg and Sharma [1] 3. Finsterer J. Neurological perspectives of neurogenic
on sudden unexplained death in epilepsy (SUDEP) in the pulmonary edema. Eur Neurol. 2019;81:94-102.
pediatric population. We have the following comments. 4. Takagi Y, Imamura T, Endo S, Hayashi K, Akiyama S, Ikuta
Y. et al. Neurogenic pulmonary edema following febrile
A pathophysiological mechanism of SUDEP not considered status epilepticus in a 22-month-old infant with multiple
by the authors is Takotsubo syndrome, also known as stunned respiratory virus co-detection: A case report. BMC Infect
myocardium or broken heart syndrome. Takotusbo syndrome is Dis. 2020;20:388.
an acute onset, usually reversible cardiomyopathy, mainly of the 5. Mahdavi Y, Surges R, Nikoubashman O, Dague KO,
left ventricle, morphologically and functionally characterized by Brokmann JC, Willmes K, et al. Neurogenic pulmonary
focal or global dyskinesia, hypokinesia, or akinesia of the left edema following seizures: A retrospective computed
ventricular myocardium, resulting in low output failure [2]. tomography study. Epilepsy Behav. 2019;94:112-17.
Though the outcome is usually fair, it can be fatal in isolated
cases, particularly in those with the global type. The syndrome AUTHORS’ REPLY
is triggered by physical or emotional stress, associated with a
massive dumping of catecholamines (catecholamine storm). It is We thank the reader for their interest in our article [1], and for
considered that the sudden overstimulation of adrenergic addressing additional putative pathophysiological
receptors on the surface of cardiomyocytes results in contractile mechanisms that may contribute to Sudden unexpected death
dysfunction and thus acute heart failure [2]. Epilepsy is the most in epilepsy (SUDEP). The authors suggest a potential role of
frequent central nervous system trigger of Takotsubo syndrome Takotsubo syndrome. Although it has been well recognised
[2]. Since it can be complicated by ventricular arrhythmias [2], that seizures may trigger this syndrome in adults, the role of
patients experiencing Takotsubo syndrome may not only die this entity in SUDEP in general continues to be debated and in
suddenly from acute heart failure but also from asystole or pediatric SUDEP, is definitely uncertain. In a review including
ventricular fibrillation [2]. 74 patients who developed Takotsubo syndrome in
association with a seizure, the age range was 18-82 years [2].
A second pathophysiological mechanism not considered is Of these, a fatal outcome occurred in only two (3%) patients.
neurogenic pulmonary edema (NPE) [3]. NPE is characterized This is similar to mortality reported in the International
by acutely developing pulmonary edema within minutes or Takotsubo registry [3]. Considering the rarity of fatality, in
hours following an acute lesion of the central nervous system association with the aforementioned age range, Takotsubo
[3], which usually resolves spontaneously within 24-48 hours syndrome seems an unlikely contributor to SUDEP
after onset [4]. Central nervous system triggers of NPE so far pathogenesis in children. Autopsy studies in SUDEP patients
reported include enterovirus 71-associated brainstem indicate that cardiac pathology comprises interstitial fibrosis,
encephalitis, subarachnoid bleeding, intracerebral bleeding, myocyte hyper-trophy as well as vascular wall thickening [4].
traumatic brain injury, stroke, hypoxia, hydrocephalus, or However, whether these are the effects of multifactorial
epilepsy, usually with generalized tonic-clonic seizures [3]. influences such as anti-seizure medications or even epilepsy
NPE may occur after a single seizure or multiple seizures. In a itself, or the cause of SUDEP remains unclear. Moreover, none
retrospective study of 47 patients, NPE was found on of these features are pathognomonic of “active catecholamine
computed tomography scans of the lungs in 19% of the myocarditis” pathology observed in TTS [5].
patients experiencing a generalized tonic clonic seizure [5].
The authors also suggest a role of neurogenic pulmonary
Overall, patients with epilepsy, particularly those with edema (NPE) in the pathogenesis of SUDEP. NPE has been
poor seizure control, polytherapy with anti-seizure drugs, consistently noted in patients with epilepsy and serves almost
poor compliance, and multiple comorbidities, should be pros- as a pathological biomarker for SUDEP. However, the reported
pectively screened for cardiac and pulmonary disease by degree of pulmonary edema has only been to a mild extent, as
electrocardiographic monitoring, echocardiography, stress observed on autopsies in the MORTEMUS study [6].
tests, and pulmonary function tests. Epilepsy patients at risk Additionally, NPE following a seizure tends to be short-lived.
of cardiac or pulmonary disease should receive primary Hence, both ante-mortem and post-mortem evidence suggest
prophylactic treatment to lower the risk of SUDEP. that NPE following seizures is a common but mild finding,
making the link between SUDEP and NPE as a causative factor
JOSEF FINSTERER,1* AND FULVIO A SCORZA2
1Klinik Landstrasse, Messerli Institute, and tenuous.
2Universidade de Sao Paulo, We agree with the authors’ suggestion that underlying
Austria, Brazil. cardiac and pulmonary diseases in persons with epilepsy,
*fifigs1@yahoo.de particularly among those who are refractory to medical

CORRESPONDENCE
therapy, should be treated. However, whether this strategy 3. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu
generates a reduction in SUDEP occurrence necessitates more DR, Jaguszewski M, et al. Clinical features and outcomes
prospec-tively collected data, particularly among children and of Takotsubo (Stress) cardiomyopathy. NEJM.
adolescents. 2015;373:929-38.
4. Nascimento FA, Tseng ZH, Palmiere C, Maleszewski JJ,
DIVYANI GARG1 AND SUVASINI SHARMA2*
Shiomi T, McCrillis A, et al. Pulmonary and cardiac
Departments of 1Neurology and 2Pediatrics,
pathology in sudden unexpected death in epilepsy
Lady Hardinge Medical College, New Delhi, India.
(SUDEP). Epilepsy Behav. 2017;73:119-25.
*sharma.suvasini@gmail.com
5. Mitchell A, Marquis F. Can Takotsubo cardiomyopathy be
REFERENCES
diagnosed by autopsy? Report of a presumed case
1. Garg D, Sharma S. Sudden Unexpected Death in Epilepsy presenting as cardiac rupture. BMC Clin Pathol. 2017;17:4.
(SUDEP) – What pediatricians need to know [published 6. Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J,
online ahead of print, 2020 Jun 12]. Indian Pediatr. Bleasel A, et al. Incidence and mechanisms of
2020;S097475591600192. cardiorespiratory arrests in epilepsy monitoring units
2. Finsterer J, Bersano A. Seizure-triggered Takotsubo (MORTEMUS): A retrospective study. Lancet Neurol.
syndrome rarely causes SUDEP. Seizure. 2015;31:84-7. 2013;12:966-77.
are shared through WhatsApp (Business). Referral to other

Telephonic Triage and Telemedicine specialties was also possible to ensure comprehensive care.
During the Peak of COVID-19 The prescription was sent to the patient as a PDF document.
After a telemedicine consultation, in case the physician felt the
Pandemic – Restricting Exposure to need of an in-person visit, the same is again indicated in the
online system and patient is allowed physical entry into the
Healthcare Professionals OPD after screening on the appointed date and time.
In our hospital, telephonic-only consults were provided to
2477 patients over a period of 45 days (21 April to 7 June,
2020) while the new system has enabled provision of care to
10,625 patients over the same time span (8 June to 16 July,
We read with interest the article by Mahajan, et al. [1] on the
2020) (Fig. 1). Physical consultations constituted only 29%
use of telemedicine during the severe acute respiratory
of the consultations in this period. This also reflects the
syndrome coronavirus 2 (SARS-CoV-2) pandemic. The
proportionate reduction in exposure of healthcare staff to
authors have well summarized the pros and cons of tele-health
potential SARS-CoV-2 carriers.
service. We would like to share our experience with
telemedicine used with forward triaging that helps mitigate The system mitigated the limitation of telemedicine by
some of its major limitations and protects healthcare workers
(HCWs) from potential exposure.
The guidelines for telemedicine have been eased to enable
continued care of non-COVID illnesses [2]. However, it is the
chronic illnesses that require holistic care by an entire
team,which have taken a backseat in the current scenario.
Telehealth needs to be part of routine practice, and not just
during emergencies [3]. This focuses on creating a more
sustainable model of care, and a telehealth-ready workforce,
incorporating telemedicine training even in the medical
curriculum [3].While many countries are using telemedicine to
triage COVID suspects, we planned to develop it into a
system of care even in the post-pandemic phase [4,5].
Following our initial experience with use of telephonic Fig. 1 Line diagram showing the number of patients seen through
new OPD system. The red line indicates the number of patients
consults, a new platform that incorporated telemedicine into
provided in-person visit after telemedicine triage. The green
the existing Hospital Information system (HIS) was launched diamonds shows the number of patients cared for- 2477 patients
on 8 June, 2020. A teleconsultation was provided as per were provided tele-consult before the launch of new platform over
schedule, once a telemedicine appointment was taken by the 45 days which increased to more than 10000 patients in next 45
patient, using a simple feature phone, any video calls or images days.

CORRESPONDENCE
allowing physical examination after adequate triaging in All India Institute of Medical Sciences,
selected patients. Although, rural India is poor in individual Jodhpur, Rajasthan, India
digital literacy, there is a wide network of e-mitra kiosks, *alizamittal@gmail.com
ASHA workers and teachers who have come forward to help REFERENCES
navigate the system and move through the process. The benefit
1. Mahajan V, Singh T, Azad C. Using telemedicine during
arising out of limited physical visits to the hospital for patient
the COVID-19 pandemic. Indian Pediatr. 2020;57:652-7.
are already described but restricting the exposure of doctors
2. Ministry of Health and Family welfare, Government of
and patients to someone who is potentially infected is of vital
India. Telemedicine Practice Guidelines Enabling
importance.
Registered Medical Practitioners to Provide Healthcare
For a major impact to be seen, an operational telehealth Using Tele-medicine. New Delhi. Available at https://
network is required, and infrastructure needs to be scaled up. It www.mohfw.gov. in/pdf/Telemedicine.pdf. Accessed on
also requires a behavior change of not just an individual or an April 03, 2020
institute but an entire health system as well as patients. We 3. Smith AC, Thomas E, Snoswell CL, et al. Telehealth for
have tried to curtail these limitations and made a beginning global emergencies: Implications for coronavirus disease
while making use of the COVID-19 crises as an opportunity to 2019 (COVID-19) [published online ahead of print, 2020
introduce the system that will stay for future. Mar 20]. J Telemed Telecare. 2020;1357633X20916567.
4. Tolone S, Gambardella C, Brusciano L, G del Genio,
Acknowledgements: Prof Kuldeep Singh, Dean Academics and
Lucido FS, Docimo L. Telephonic triage before surgical
Prof Sanjeev Misra, Director, AIIMS, Jodhpur for conceptua-
ward admission and telemedicine during COVID-19
lizing the idea and facilitating the development of the software.
outbreak in Italy. Effective and easy procedures to reduce
in-hospital positivity. Int J Surg. 2020; 78:123-25
ALIZA MITTAL1*AND PUNEET PAREEK2 5. Hollander JE, Carr BG. Virtually perfect? Telemedicine
Departments of 1Pediatrics and 2Radiation Oncology,
muscular dystrophy and limb girdle muscular dystrophies) and

Proximal Limb Girdle Weakness, SMA type 3. It may be difficult to differentiate these conditions
Joint Hyperlaxity, and preserved based on deep tendon jerks and creatine kinase levels because
these are often misleading. Deep tendon reflexes may be
Deep Tendon Reflexes: A preserved in SMA type 3 [1]. Joint hypermobility and
hyperlaxity, although an overlooked feature of SMA, if present
Distinctive Phenotype favors a diagnosis of SMA over muscular dystrophy [2,3]. The
caveats include early-onset muscle disorders such as congenital
muscular dystrophies and congenital myopathies [2]. In SMA,
A 9-year-old girl presented with mild motor delay and
progressive proximal limb-girdle weakness. Socio-cognitive
milestones were normally attained. Examination revealed
normal head size and intellectual functioning, proximal limb
girdle weakness, mildly prominent calves, and preserved deep
tendon jerks (including both ankles). She had hyperlaxity of
finger joints and both elbow joints (Beighton score 4/9). She also
had polyminimyoclonus. Creatine kinase levels were elevated
(790 IU/L) while electrocardiogram revealed tremor (Fig. 1).
Nerve conduction studies revealed motor axonal loss with
sensory sparing while electromyography (EMG) was
suggestive of abnormal spontaneous activity (fibrillations and
fasciculations) signifying active denervation. She was not
cooperative for voluntary EMG assessment. Multiplex
ligation-dependent probe amplification (MLPA) revealed
homozygous deletion of exon 7 and 8 of SMN1 gene confirming
the diagnosis of spinal muscular atrophy type 3 (SMA type 3).
Important differential diagnosis for progressive limb girdle Fig. 1 Electrocardiogram of the index patient showing the high
weakness presenting in late childhood (with onset beyond frequency (30-40 Hz) tremor (arrows) due to muscle
infancy) include muscular dystrophies (especially Duchenne fasciculations (seen predominantly in limb leads).

CORRESPONDENCE
anterior horn cell loss begins in early infancy and may possibly REFERENCES
account for distal hypotonia and hyperlaxity. Hyperlaxity,
1. Lannaccone ST, Browne RH, Samaha FJ, Buncher
especially of upper limb joints may persist till adulthood in
CR. Prospective study of spinal muscular atrophy before
more than half of patients [4]. It is perplexing to see that this
age 6 years. Pediatr Neurol. 1993;9: 187-93.
finding was not captured in major prospective cohorts of SMA
2. Donkervoort S, Bonnemann CG, Loeys B, Jungbluth H,
type 2 and 3, which predominantly addressed the weakness and
Voermans NC. The neuromuscular differential diagnosis of
ambulation. This finding needs to be further confirmed in large
joint hypermobility. Am J Med Genet C Semin Med Genet.
cohorts not only because of diagnostic significance but also for
2015;169C:23-42.
rehabilitation point of view, considering the improved outcomes
3. Haaker G, Fujak A. Proximal spinal muscular atrophy:
with newer therapies in SMA.
Current orthopedic perspective. Appl Clin Genet.
PRIYANKA MADAAN AND LOKESH SAINI* 2013;6:113-20.
Pediatric Neurology Unit, Department of Pediatrics, 4. Tofts LJ, Elliott EJ, Munns C, Pacey V, Sillence DO. The
Postgraduate Institute of Medical Education and Research, differential diagnosis of children with joint hypermobility: A
Chandigarh, India. review of the literature. Pediatr Rheumatol Online J.
*drlokeshsaini@gmail.com 2009;7:1.
resuscitation was developed. The 15-minute simulation was run

NeoBox - A Multipurpose Aerosol with two resident doctors, an embedded simulation nurse, and a
Box for Neonatal Care low fidelity manikin in the delivery room setting. The ‘newborn’
was a low fidelity simulator (Laerdal Medical). During
DuringCOVID-19 Pandemic simulation sessions, accessing the neonate and performing
resuscitation steps in the squared aerosol box was observed to
be impossible. After completion of each session, the learners
were debriefed using the PEARLS Healthcare Debriefing Tool
with plus/delta and advocacy enquiry format by a trained
simulation leader [8,9]. Difficulties were encountered at all
Safety of the newborn and the protection of healthcare workers
steps of resuscitation like - attaching pulse oximeter, performing
(HCWs) from aerosol exposure are extremely important during
positive pressure ventilation, intubation, chest compression
the current severe acute respiratory illness coronavirus 2
and umbilical catheterization, etc. These difficulties were
(SARS-CoV-2) pandemic. Use of personal protective
addressed and the need for a modified aerosol box for neonates
equipment (PPE) has been shown to be associated with a
was informed to the biomedical department of our institute. The
reduced risk of infection [1]. As per WHO guidelines, it is
box underwent multiple modifications based on the feedbacks
mandatory to use personal protective equipment (PPE) while
received. The final design specifications were given (Web Table
performing aerosol-generating procedures like suction,
I) and the NeoBox was developed (Fig.1).
intubation, chest compression etc. [2,3]. However, despite the
use of PPE, there remains a possibility that aerosols can The NeoBox is made up of a transparent polycarbonate (3
contaminate nearby surfaces [4]. An aerosol box acts as a mm thick). The material required was procured and necessary
physical barrier against the aerosol spread [4,5]. PPE with a fabrications were done by the local acrylic / polycarbonate sheet
barrier enclosure like an aerosol box can be an effective measure fabricator. The average time required to make one NeoBox was
to minimize aerosol spread and exposure during this pandemic approximately 4 hours. The cost was Rs 6500. An alcohol based
[2,4]. disinfectant (Ethanol 70%) with a contact time of minimum 1
minute is used to clean the NeoBox [10].
Recent literature reports that when an aerosol box was used
for airway management, the inner surface of the box and the The NeoBox was primarily designed as a physical barrier to
laryngoscopist’s gloves and gowned forearms were observed to prevent aerosol exposure and spread while performing aerosol-
be contaminated [4], but no macroscopic contamination outside generating procedures during resuscitation in delivery room.
the box was observed [4]. Unlike adult resuscitation, the focus While running simulation sessions, its wider application for
of newborn resuscitation is effective ventilation of baby’s lungs neonatal care like transporting a suspected or confirmed
which includes aerosol-generating procedures like suction, PPV, COVID-19 neonate from one place to another (intra hospital
using continuous positive airway pressure, intubation, chest transport) and caring for them in the neonatal intensive care unit
compression, etc. [6,4]. To see the feasibility of using the (NICU) while performing aerosol-generating procedures was
standard aerosol box as a barrier enclosure while performing recognized. Use of NeoBox in addition to PPE helped boosting
aerosol-generating procedures on neonates, a novel simulation HCWs confidence for managing suspected or confirmed
session integrating a newborn delivery of a suspect or confirmed COVID-19 neonates. We found that the NeoBox would require
COVID-19 mother with a subsequent need for neonatal training before use in the treatment of patients. Wearing PPE is

CORRESPONDENCE
Fig. 1 NeoBox with dimensions. Fig.2 NeoBox in delivery room – resuscitator managing airway.
must for HCWs while performing aerosol-generating 3. Harding H, Broom A, Broom J. Aerosol generating
procedures in a suspected or confirmed COVID-19 neonate. procedures and infective risk to healthcare workers: SARS-
NeoBox works as a physical barrier to prevent aerosol spread. CoV-2 - the limits of the evidence. J Hosp Infect.
However, in case of difficulty it is advised to remove the 2020;105:717-25. Epub ahead of print.
NeoBox and perform intubation. 4. Canelli R, Connor CW, Gonzalez M, Nozari A, Ortega R.
Barrier enclosure during endotracheal intubation. N Engl J
We propose the NeoBox as an additional protection, and
Med. 2020;382:1957 8.
suggest that it may be considered to be an adjunct to standard
5. Motara F, Laher AE, Du Plessis J, Moolla M. The
PPE for managing suspected COVID-19 newborns in delivery
“Intubox”: Enhancing Frontline Healthcare Worker Safety
room (Fig. 2). It can also be used as a barrier enclosure during
During Coronavirus Disease 2019 (COVID-19). Cureus.
intrahospital transport and while performing aerosol-generating
2020;12:e8530.
procedures in the NICU.
6. Chandrasekharan P, Vento M, Trevisanuto D, Partridge E,
Acknowledgment: Dr Vaibhavi Upadhye, DrArti Rajhans and Underwood MA, Wiedeman J, et al. Neonatal resuscitation
DrDhananjay Kelkar from Deenanath Mangeshkar Hospital for and postresuscitation care of infants born to mothers with
their support and guidance. suspected or confirmed SARS-CoV-2 infection. Am J
Published Online: August 10, 2020; PII: S097475591600228. Perinatol 2020;37:e3-e3.
7. Edelson DP, Sasson C, Chan PS, Atkins DL, Aziz K, Becker
SHILPA KALANE,1* NIRANJAN KHAMBETE2 AND LB, et al. American Heart Association ECC Interim COVID
RAJAN JOSHI3 Guidance Authors. Interim Guidance for Basic and
Departments of 1Neonatology and 3Pediatrics, Advanced Life Support in Adults, Children, and Neonates
and 2Clinical Eningeering, With Suspected or Confirmed COVID-19: From the
DeenanathMangeshkar Hospital, Pune 411004, Emergency Cardiovascular Care Committee and Get With
Maharashtra, India. The Guidelines-Resuscitation Adult and Pediatric Task
*drshilpakalane@gmail.com Forces of the American Heart Association. Circulation.
2020;141:e933-43.
REFERENCES
8. Bajaj K, Meguerdichian M, Thoma B, Huang S, Eppich W,
1. Chou R, Dana T, Buckley DI, Selph S, Fu R, Totten AM. Cheng A. The PEARLS healthcare debriefing tool. Acad
Epidemiology of and risk factors for coronavirus infection in Med. 2018;93:336.
health care workers: A living rapid review. Ann Intern Med. 9. Rudolph JW, Simon R, Rivard P, Dufresne RL, Raemer DB.
2020;173:120-36. Debriefing with good judgment: Combining rigorous
2. World Health Organization. Infection Prevention and feedback with genuine inquiry. Anesthesiol Clin.
Control During Health Care When COVID-19 is Suspected: 2007;25:361 76.
Interim Guidance. 19 March 2020. Available from: https:// 10. World Health organization. Cleaning and Disinfection of
www.who.int/publications-detail/ infection-prevention-and- Environmental Surfaces in the Context of COVID-19.https:/
control-during-health-care-when-novel-coronavirus- /www.who.int/publications-detail/cleaning-and-disinfection-
(ncov)-infection-is-suspected-20200125. Accessed May 23, of-environmental-surfaces-inthe-context-of-covid-19.
2020. Accessed May 23, 2020.

CORRESPONDENCE
[2]. The common causes of peripheral hypotonia with elevated

An Infant With Isolated Motor CPK levels in infants include congenital muscular dystrophy
Delay (CMD), congenital myopathies (central core and multiminicore
myopathy), and metabolic myopathies like Pompe’s disease
[3]. Children with congenital muscular dystrophy usually have
much higher serum CPK levels with hypotonia, while children
with secondary merosin deficient CMD often have epilepsy,
cognitive impairment to some extent and brain malformations.
An 11-month-old male infant, first born of a non- Children with congenital myopathies have predominantly
consanguineous marriage was brought with concerns of delayed ocular, facial and bulbar involvement along with mildly elevated
motor milestones. He had an uneventful antenatal and perinatal serum CPK. Infants with Pompe disease have hepatomegaly
period. He achieved head control at 6 months of age and rolling and cardiomyopathy along with peripheral hypotonia and
over at 10 months of age. He had normal social and cognitive elevated CPK levels. Infantile polymyositis is another rare
milestones. None of the family members in a three-generation possibility in such cases, which unlike older children, may
pedigree had symptoms suggestive of any neuromuscular sometimes present with isolated motor delay and elevated
illness. On examination, he had peripheral hypotonia, serum CPK without any fever or systemic features.
diminished deep tendon reflexes in both upper and lower limbs,
without any tongue fasciculation or signs of facial, extraocular, Early diagnosis of DMD often provides an opportunity for
bulbar, and cardiac muscle involvement. Serum creatinine timely institution of treatment including drugs like steroids,
phosphokinase was found to be elevated (2568 IU/L). A clinical ataluren and eteplirsen, physiotherapy and genetic counselling
possibility of Pompe disease, congenital muscular dystrophies of parents for subsequent conceptions [4]. Early institution of
and congenital myopathies (central core and multiminicore glucocorticoids in low doses, as soon as the diagnosis is
myopathy) was considered. Muscular dystrophy and con- established, has been shown to improve the outcome at the cost
genital myopathy genetic panel revealed a hemizygous of tolerable side effects, although not able to cure the disease.
pathogenic nonsense variation in exon 61 of the DMD gene Glucocorticoids were initiated in the index case after discussing
(ChrX:g:31366736G>A), confirming a diagnosis of Duchenne risks and benefits with parents.
muscular dystrophy (DMD). The observed variation was To conclude, while evaluating an infant with raised CPK
confirmed by sanger sequencing. It found to be previously levels, clinicians should consider DMD as one of the differential
reported in patients with DMD and has been classified as diagnosis apart from CMD and few selected congenital
pathogenic in ClinVar database. The in silico prediction of the myopathies. Early diagnosis and initiation of steroids may
variant was damaging by Mutation Taster 2. He was started on improve the outcome at the cost of tolerable side effects.
oral prednisolone (0.3mg/kg/day) and physiotherapy and
parents were counseled about the nature and prognosis of the INDAR KUMAR SHARAWAT AND PRATEEK KUMAR PANDA*
disease. Pediatric Neurology Division, Department of Pediatrics,
All India Institute of Medical Sciences,
Duchenne muscular dystrophy (DMD) is the commonest
Rishikesh, Uttarakhand. India.
muscular dystrophy having an incidence rate of one in every *drprateekpanda@gmail.com
3500 male infants [1]. Indian data suggests that exonic deletions
REFERENCES
and duplications are found in around 67% and 6% boys with
DMD, respectively. Most of the cases become symptomatic 1. Thangarajh M. The Dystrophinopathies. Contin Minneap
between 2 to 6 years of age, with frequent falls during walking, Minn. 2019;25:1619-39.
difficulty in getting up from sitting or squatting position, and 2. Tallapaka K, Ranganath P, Ramachandran A, Uppin MS,
waddling gait [1]. However, few recent studies have revealed Perala S, Aggarwal S, et al. Molecular and histopathological
that a proportion of children with DMD had a delay in the characterization of patients presenting with the duchenne
attainment of motor milestones from infancy [2]. Although muscular dystrophy phenotype in a tertiary care center in
some of these parents often express the developmental concern Southern India. Indian Pediatr. 2019;56:556-59.
of their children in toddler years, differential diagnosis of DMD 3. Leyenaar J, Camfield P, Camfield C. A schematic approach
is rarely considered in these children because of the absence of to hypotonia in infancy. Paediatr Child Health. 2005;10:397-
muscle weakness [2]. In the existing literature, the youngest age 400.
at which diagnosis was established in symptomatic DMD cases 4. Mah JK. Current and emerging treatment strategies for
was 3 years of age, although new-born screening and screening Duchenne muscular dystrophy. Neuropsychiatr Dis Treat.
of affected siblings have detected asymptomatic cases in infants 2016;12:1795-8.

CORRESPONDENCE
wards recently. As a pediatrician, our primary responsibility is

Therapeutic Clowning in Pediatric better health and quality of life of our pediatric patients, and
Practice: A Novel Concept to Think hence, this novel idea of therapeutic clowning is worth trying,
especially to begin with vaccination sessions. Further research
About in India is warranted to replicate its results in the Indian settings.
Published Online: September 05, 2020: PII: S097475591600239.
SHAHID AKHTAR SIDDIQUI* AND MUKESH VIR SINGH

Therapeutic or medical clowning is a new concept across
Department of Pediatrics,
various healthcare settings around the world [1]. It is a para-
SN Children Hospital, MLN Medical College,
medical practice in which clowns are associated with healthcare
Allahabad, Uttar Pradesh, India.
system to mitigate anxiety, stress, fear and sadness in admitted *sha.akht@yahoo.com
patients, thereby augmenting the healing process [2]. They
REFERENCES
create a more positive and constructive hospital environment
and trust between patients and medical teams. Research has 1. Finlay F, Baverstock A, Lenton S. Therapeutic clowning in
concluded that medical clowns have a significantly positive paediatric practice. Clin Child Psychol Psychiatry. 2014;
effect in adults [3]. A consistent observation has been seen that 19:596-605.
clowns are always appreciated by pediatric patients [4]. 2. Nuttman-Shwartz O, Scheyer R, Tzioni H. Medical
clowning: even adults deserve a dream. Soc Work Health
Idea of medical clowning was conceptualized by Michael
Care. 2010;49:581-98.
Christensen in 1986, in the United States. At a physiological
3. van Venrooij LT, Barnhoorn PC. Hospital clowning: A
level, laughing stimulates release of endorphins modulating
paediatrician’s view. Eur J Pediatr. 2017;176:191 97.
immune system. Laughing also replaces negative feeling with
4. Barkmann C, Siem A-K, Wessolowski N, Schulte-
positive ones at and emotional level. Clowning distracts the
Markwort M. Clowning as a supportive measure in
child from the current situation at the cognitive level. Socially,
paediatrics – A survey of clowns, parents and nursing staff.
laughing stimulates better interaction between children and
BMC Pediatr. 2013;13:166.
health care personnel [4,5].
5. Bennet MP, Lengacher C. Humor and laughter may influence
This practice is still nascent at present in India. Sir JJ health: III. Laughter and health outcomes. Evid Based
Hospital Mumbai has begun with medical clowning in pediatric Complement Alternat Med 2007; 5:37-40.
We concur with the authors that the role for specific

Multisystem Inflammatory cytokine blockade including use of biologics in MIS-C is still
Syndrome in Children (MIS-C) - lacking. The ACR guidelines advice immunomodulatory
therapy for all severe/critical MIS-C patients with shock,
Recent Updates significant respiratory distress, neurologic changes,
dehydration, or features of KD. IVIG and glucocorticoid remain
first line agents either alone or in combination. Anakinra is safe
in severe infections among children with hyper-inflammatory
We read the very timely article by Bhat, et al. [1] providing syndromes. Although tocilizumab is effective in reducing
valuable insights into clinical epidemiology of multisystem mortality and ICU admission in patients with severe COVID-
inflammatory syndrome in children (MIS-C). We comment on 19 pneumonia [2], the clinical evidence is insufficient regarding
the recent evidence to complement the information provided. its efficacy and safety for COVID-19 because of concerns
regarding risk of secondary bacterial and fungal infections [5].
Recent clinical guidelines by American College of Aspirin (3-5 mg/kg/day) should be used in patients with MIS-C
Rheumatology (ACR) elaborate on the most appropriate and KD-like features and/or thrombocytosis and continued until
diagnostic and therapeutic steps for MIS-C at the present time, normali-zation of platelet count and confirmed normal coronary
advising inflammatory markers and cytokine panel testing [2]. arteries at ≥4 weeks after diagnosis. Anticoagulation with
There is noteworthy discordance in interleukin levels of IL-1, enoxaparin should be added in patients with coronary artery
IL-6 and IL-10 among patients with Kawasaki disease (KD) vs aneurysm and Z score ≥10.0 or an ejection fraction (EF) <35%
MIS-C [3]. While IL-1 is the main mediator of coronary artery [2], but despite benefits, strategy based evidence is required due
inflammation in KD, inflammatory process in MIS-C is to high risk of hemorrhagic events or complications.
predominantly driven by IL-6 and IL-10, which may play a role
in the myocardial dysfunction and higher severity of the 2019- With the availability of these guidelines a standardized
nCoV infection [4]. treatment plan for MIS-C involving multidisciplinary care

CORRESPONDENCE
under pediatric cardiology, infectious disease, intensive care and 2. Henderson LA, Canna SW, Friedman KG, et al. American
rheumatology specialists can be designed. As the evidence base College of Rheumatology Clinical Guidance for Pediatric
for COVID-19 and MIS-C treatment and care management is Patients with Multisystem Inflammatory Syndrome in
evolving rapidly, this guidance may change in future. Children (MIS-C) Associated with SARS-CoV-2 and
Hyper Inflam-mation in COVID-19. Version 1 [published
MANGLA SOOD1 AND SEEMA SHARMA2*
online ahead of print, 2020 Jul 23]. Arthritis Rheumatol.
From 1Departments of Pediatrics,
2020;10.1002/art.41454.
Indira Gandhi Medical College, Shimla; and
2Dr Rajendra Prasad Government Medical College, 3. Li H, Chen K, Liu M, Xu H, Xu Q. The profile of peripheral
blood lymphocyte subsets and serum cytokines in children
Kangra at Tanda; Himachal Pradesh, India.
*seema406@rediffmail.com with 2019 novel coronavirus pneumonia. J Infect. 2020;
81:115-20.
REFERENCES
4. Shulman ST. Pediatric coronavirus disease-2019-associated
1. Bhat CS, Gupta L, Balasubramanian S, Singh S, Ramanan A multisystem inflammatory syndrome. J Pediatric Infect Dis
V. Hyper inflammatory syndrome in children associated Soc. 2020;9:285-6.
with COVID-19: Need for awareness [published online 5. Cortegiani A, Ippolito M, Greco M, et al. Rationale and
ahead of print, 2020 Jul 15]. Indian Pediatr. 2020; evidence on the use of tocilizumab in COVID-19: A
S097475591600208. systematic review. Pulmonol. 2020;S2531-0437:30153-7.
during the lockdown. In the pre lockdown period, the number of

Impact of the COVID-19 Pandemic babies screened in the OPD were significantly higher than those
on Retinopathy of Prematurity screened inside the institute NICU/neonatal nursery (P=0.001),
which was also reversed during the lockdown period.
Practice: An Indian Perspective
Impact on ROP treatment: Laser photocoagulation was
increasingly preferred (49 eyes) over intravitreal anti-vascular
endothelial growth factor (anti-VEGF) agents (2 eyes) as the
primary treatment during the lockdown period. The main reason
for this was the finite nature of laser photocoagulation com-
The severe acute respiratory syndrome coronavirus 2019 pared to the risk of recurrences with anti-VEGF agents, which
(SARS-Cov-19) associated lockdown in India led to cessation of requires regular and extended follow-up [4]. We had at least
public transport and routine outpatient department (OPD) three babies with aggressive posterior retinopathy of pre-
services. However, the need to screen to premature babies for maturity (APROP) who were given anti-VEGF injection prior
retinopathy of prematurity (ROP) continued, with reduction in to lockdown and missed follow-up for two months owing to
those actually getting screened. ROP requires urgent treatment movement restrictions during lockdown. While the disease
and has been listed as an essential medical service during the regressed in two of these babies, one progressed to develop
COVID-19 pandemic by both the American Academy of tractional retinal detachment in both eyes and required surgical
Ophthalmology and All India Ophthalmological Society [1-3]. intervention. In the pre-lockdown period, all laser treatments
We discuss the impact of the COVID-19 pandemic on ROP (for outborns as well as inborns) were done inside the neonatal
services experienced at our center. nursery/NICU of our institute under monitoring by a neo-
natologist. This sometimes entailed a wait period of 24-48 hours
Impact on ROP screening: Following the guidelines issued by
depending on availability of a monitoring bed in the NICU.
the All India Ophthalmological Society (AIOS) in conjunction
During the lockdown, there was shut down of most elective
with the Vitreo Retina Society of India (VRSI) and the Indian
procedures such as cataract surgery. This allowed availability of
Retinopathy of Prematurity (iROP) Society, we continued to
more operation theatre (OT) tables for emer-gency procedures.
screen premature babies for ROP [2,3]. Being a tertiary care
We therefore arranged to perform all ROP interventions in the
institute, we are the primary referral center for neighboring
OT itself with the focus being on same day treatment. A
states. However, given the scarcity of trained ophthalmologists
pediatrician was available on call for monitoring in addition to
to perform ROP screening, we often end up as the first point of
the anesthetist. This helped reduce the contact of outborns with
screening for majority of the regional neonatal intensive care
inborns as well as other NICU healthcare professionals in
units (NICU). There was a decrease in the number of infants
addition to reducing the waiting time. All lasers were performed
screened both in the OPD (396 vs 87; P=0.001) as well as in the
under topical anesthesia using personal protective equipment as
institute NICU (241 vs 169; P=0.001) during similar time
per the AIOS guidelines [2,5].
periods pre (1st January, 2020 to 23 March, 2020) and post (24
March, 2020 to 31 May, 2020) COVID-19 lockdown. This Impact on surgical rate: The proportion of babies requiring lens
could primarily be attributed to the lack transport facilities for sparing vitrectomy (LSV) as the primary intervention increased
patients to reach the hospital, despite this being permitted from 1.1% in the pre-lockdown period to 2.9% in the post-

CORRESPONDENCE
lockdown period. Majority had stage 4A ROP (1, bilateral stage Ramanadhane, Dr Atul Arora, Dr Uday Tekchandani, and Dr
4B ROP). Delayed screening, delayed referral and travel Anchal Thakur for their help in managing ROP patients during the
difficulties were probably responsible for this advanced presen- pandemic.
tation. For bilateral cases, immediate sequential bilateral vitreous Published Online: September 05, 2020: PII: S097475591600240.
surgery was preferred over multiple sessions of surgery [6].
DEEKSHA KATOCH,1 SIMAR RAJAN SINGH1* AND
Impact on incidence of conjunctivitis: ROP screening and PRAVEEN KUMAR2
treatment requires frequent contact with the eyelids, both by Departments of 1Ophthalmology and 2Neonatology,
the ophthalmologist as well as the parents. This increases the Advanced Eye Centre,
chances of conjunctivitis in these babies [7]. Prior to COVID-19 Post Graduate Institute of Medical Education and Research,
lockdown, 30 babies developed conjunctivitis while on follow Chandigarh, India.
up, including a cluster of 24 babies in the institute’s NICU/ simarrajansingh@gmail.com
neonatal nursery. Post-lockdown, this number came down to
three. Overall conjunctivitis infection rate reduced from 4.7% to REFERENCES
1.2% (P=0.01). This could primarily be attributed to the
1. American Academy of Ophthalmology. 2020, March 27.
enforcement of frequent handwashing practices amongst both
List of urgent and emergent ophthalmic procedures.
the doctors as well as the caregivers. We also reduced the points
Available from: https://www.aao.org/headline/list-of-urgent-
of contact of the baby once in the hospital. All babies for ROP
emergent-ophthalmic-procedures. Accessed June 09, 2020.
screening were managed at a single dedicated room without going
2. Sengupta S, Honavar SG, Sachdev MS, Sharma N, Kumar A,
through the general ophthalmic screening OPD. Parents were
Ram J, et al. All India Ophthalmological Society - Indian
educated and encouraged to dilate their babies’ eyes themselves
Journal of Ophthalmology consensus statement on preferred
after performing hand hygiene while in the hospital waiting area.
practices during the COVID-19 pandemic. Indian J
This helped reduce number of contacts with the health care
Ophthalmol. 2020;68:711-24.
professionals.
3. Gupta V, Rajendran A, Narayanan R, Chawla S, Kumar A,
Implications for future: There were several important lessons Palanivelu MS, et al. Evolving consensus on managing vitreo-
learnt from the above experience. Firstly, there is a need to retina and uvea practice in post-COVID-19 pandemic era.
expand tele-medicine services for ROP throughout the country. Indian J Ophthalmol. 2020;68:962-73.
Fundus photographs taken by a trained nurse/technician using 4. Singh SR, Katoch D, Handa S, Kaur S, Moharana B, Dogra
portable, wide-field camera system scan be sent to a remotely M, Dogra MR. Safety and efficacy of 532 nm frequency
placed expert and advice regarding the urgency of referral can be doubled Nd YAG green laser photocoagulation for treat-
given. It will also be a good tool to educate parents regarding the ment of retinopathy of prematurity. Indian J Ophthalmol.
condition of their child’s eye. Low-cost imaging devices being 2019;67:860-5.
made available now are a step in this direction [8]. Secondly, 5. Jalali S, Azad R, Trehan HS, Dogra MR, Gopal L, Narendran
there is an urgent need to ensure adequate training for indirect V. Technical aspects of laser treatment for acute retinopathy
ophthalmoscopy during residency at all medical colleges in the of prematurity under topical anesthesia. Indian J
country which would help in bringing out more Ophthalmol. 2010;58:509-15
ophthalmologists who are confident in this field. Thirdly, laser 6. Yonekawa Y, Wu WC, Kusaka S, Robinson J, Tsujioka D,
photocoagulation for the treatment of ROP may be a better Kang KB, et al. Immediate Sequential Bilateral Pediatric
alternative in these times when there is a doubt on the ability of Vitreoretinal Surgery: An International Multicenter Study.
the patient to follow-up regularly. Lastly, some of the positive Ophthalmology. 2016;123:1802-08.
habits like frequent handwashing and use of masks may be a 7. Ersoy Y, Otlu B, Türkçüoglu P, Yetkin F, Aker S, Kuzucu
boon even in the post-COVID era, if reinforced regularly. They C. Outbreak of adenovirus serotype 8 conjunctivitis in
potentially helped reduce the conjunctivitis infection rate in our preterm infants in a neonatal intensive care unit. J Hosp
setting and could have similar implications in other healthcare Infect. 2012;80:144-49.
settings. We hope our experience would assist other centers 8. Vinekar A, Rao SV, Murthy S, Jayadev C, Dogra MR, Verma
managing ROP, as we continue to experience the impact of the A, et al. A Novel, Low-Cost, Wide-Field, Infant Retinal
COVID-19 pandemic. Camera, ‘Neo’: Technical and Safety Report for the Use on
Acknowledgements: Dr Vipin Rana, Dr Raghulnadhan Premature Infants. Transl Vis Sci Technol. 2019; 8:2.

CORRESPONDENCE
Web Table I Difficulties Encountered by Learners During Simulation Sessions and Development of NeoBox
Simulation Delta Development of NeoBox
scenario
Scenario 1 Size of the box was too big to fit under NeoBox’s base dimensions were determined by taking measurements of
radiant warmer warmer bed (NeoBox base dimensions : Warmer bed length - 10 cm, Warmer
bed breadth - 10 cm)
Scenario 2 Difficulty in accessing newborn’s air- The aerosol box was flattened and angulated at the top to provide clear
way due to the straight front surface. vision to the person performing intubation.
Difficult to access newborn’s airway The lower border of two semicircular ports on the front side was lowered.
due to it’s inconveniently located ports
Scenario 3 Need for extra ports on both sides in Two ports were incorporated on either side of the box. The distal port was
case baby needs advanced resuscitation designed to be bigger (oval in shape) than the proximal one (circular in
shape) for the easy access during procedures.
Confusion in positions of the resusci- If the baby needs initial steps of resuscitation: The resuscitator stands at
tator while performing resuscitation the head end and the assistant if any stands on the right side.
If the baby needs advanced steps of resuscitation:
(i) Instead of AMBU bag, T piece resuscitator will be used as the bag
would need lot of space.
(ii) Intubation will be performed from the head end.
(iii) The resuscitator will shift to the left side while providing PPV through
ET.
(iv) Second resuscitator will provide chest compressions from head end.
(v) Third resuscitator will perform umbilical catheterization from right side
Scenario 4 How to cover ports to minimize aerosol Polycarbonate flaps were prepared to cover side ports and a square
spread during intra hospital transport? polycarbonate sheet was made to cover front side. One can use
polyethylene wrap to cover the ports and front side.
INDIAN PEDIATRICS VOLUME 57__OCTOBER 15, 2020

NEWS IN BRIEF
Infections in the time of the pandemic using AI systems for diagnosis, but are these RCTs designed
appropriately factoring in the complexities of AI and can we take
The COVID-19 pandemic is an evolving natural experiment. their evidence at face value?
There has been an unexpected windfall in this time of despair.
Researchers from the Boston Children’s Hospital have analyzed Guidelines for clinical trial protocols evaluating
the rates of 12 common childhood infections in the same calendar interventions with an AI component (SPIRIT- AI) and trial reports
period during ‘social distancing’ and in the ‘pre-social distancing with AI (CONSORT- AI) have recently been published. One of the
era,’ using data of a primary care network which caters to 375,000 issues is random alerts by AI algorithms which will falsely over
children. The infections they studied were acute otitis media detect abnormalities compared to a clinician and be labelled as
(AOM), bronchiolitis, common cold, croup, gastroenteritis, ‘better’. Another major issue with AI are that many systems are
influenza, nonstreptococcal pharyngitis, pneumonia, sinusitis, self-learning and continually changing. Further the people who
skin and soft tissue infections (SSTIs), streptococcal pharyngitis, create the algorithms are not the clinicians who see patients. So
and urinary tract infection (UTI). All infections showed a they need to have a deeper understanding of medicine and
remarkable decline. Influenza, croup and bronchiolitis practically clinicians need to have a better understanding of what these
disappeared. The least decline was in the rates of UTI, which was algorithms may or may not handle. The new guidelines have asked
as expected. for clear detailing of the type of AI model being used, which
version of the algorithm will be used, specific plans to identify
The decline in infections may have been due to decrease in and analyze performance errors etc.
prevalence or a choice not to seek medical care. However the
trends of change in UTI suggest that the former was more Some paths in medicine are so byzantine, that even ‘angels
predominant. It may give good pointers in developing strategies to would fear to tread’. And the guidelines to rein in AI in medicine
reduce common childhood infections after the pandemic is are certainly one of them.
resolved. (BMJ 9 September 2020)
(Pediatrics 2 September 2020)
AAP guidelines for resistance training in children
Deconstructing motherhood
It is well established that muscular fitness in children is declining
Where in the brain is the center for nurturing? Catherine Dulac, a worldwide. On the other hand, competitive training in sports is
molecular biologist at Harvard, has won $3 million dollars as part starting at earlier ages and resistance training for body image
of the Breakthrough Prize for work in this esoteric field. She has development is not uncommon in some children.
discovered the neural circuits which explain the unique parental
The American Academy of Pediatrics has brought out
behaviors in males and females. Close observation in mice
guidelines to help pediatricians counsel parents in this regard.
showed that female mice show remarkable stereotyped behaviors
Resistance training/weights is now considered to have several
when they see baby mice. Even when they are not the mother, they
benefits even in children e.g., improvements in motor skills,
immediately retrieve the pups, groom them, build a nest for them
enhancement of bone mineral density and reduction in injuries.
and crouch around them. In sharp contrast in normal
Supervision under a trainer is preferred. Children recover quickly
circumstances, male mice will attack baby mice.
from resistance training fatigue, hence shorter resting periods of 1
Dulac’s group found that the medial preoptic area of the minute between sets initially and 2-3 minutes later is
hypothalamus releases a molecule called galanin which recommended.
orchestrates the various parenting behaviors. Stimulating the
Pre-habiliation is a term used for children in competitive
galanin neutrons with light caused the male mice to show unusual
sports. It means prophylactic exercises to prevent injuries. The
maternal parenting behaviors. Destroying the preoptic areas in
other technique is plyometric exercises. This involves repetitive
females resulted in non-nurturing behaviors in females.
concentric exercises to rapidly build strength. Children as young
The work is extraordinary because it is the first time such a as five can build strength with one-legged hops or frog jumps. For
complex social behavior like parenting has been explored to the older children, lifting weights can be combined with aerobics or
cellular level. The biological underpinnings of social behaviors other sports to round out their activities. Children with
may open doors to therapeutics in many complex problems like uncontrolled hypertension may need prior medical evaluation.
post-partum depression, drug addiction and criminality.
The AAP also recommends 1-2 days off per week to prevent
(Nature News 10 September 2020)
injuries due to over training. We also need to make sure that
Treading softly - CONSORT-AI guidelines children take adequate fluids and calories required for the
increased expenditure.
Artificial intelligence (AI) systems are sweeping across the (Pediatrics June 2020)
landscape of medicine. And we stand mostly unprepared. GOURI RAO PASSI
Recently there has been a spate of randomized controlled trials gouripassi@gmail.com

CL I P P I N G S
Theme: Genetics
Exome sequencing aids in the treatment of a child with Ultra-rapid exome sequencing in critically ill children
type I interferonopathy (N Engl J Med. 2020; 382(3):256-65) with monogenic conditions (JAMA. 2020;323:2503-11)
Ubiquitin-specific protease 18 (USP18) deficiency [Pseudo- This study was conducted in Australia to evaluate the utility of
TORCH syndrome 2 (MIM# 617397)], due to homozygous or ultra-rapid exome sequencing in critically ill pediatric patients
compound heterozygous variants in USP18, is a severe with suspected monogenic diseases. A total of 108 patients were
monogenic autoinflammatory disorder. USP18 restricts the recruited prospectively from neonatal and pediatric intensive
access of Janus-associated kinase 1 (JAK1) to type I interferon care units from March, 2018 to February, 2019. Trio exome
receptor, thus preventing excessive interferon signaling. sequencing was performed in 105 families and singleton exome
Individuals with USP18 deficiency present in the neonatal was performed in three families. The median age of study
period with intracranial calcification, hemorrhage, liver participants was 28 days (range 0-17 years). 62 patients were
dysfunction, septic shock, and thrombocytopenia, resembling from NICU (57%), 36 from PICU (33%) and 10 were from
congenital intrauterine infections. A Saudi Arabian boy, born to other hospital wards. The majority of patients had neurological
first-cousin parents, and diagnosed in the first month was symptoms like seizures or hypotonia. The mean time from
treated with oral ruxolitinib, a JAK1/2 inhibitor. The child sample receipt to the generation of a report (primary outcome)
showed clinical improvement and was discharged from the was 3.3 days (95% CI, 3.2-3.5 days). Fifty-six genetic
intensive care unit at 9 months. At 3 years of age, this child is the conditions were diagnosed in 55 patients (51%). Two novel
oldest surviving individual with this rare condition. The case candidate genes were identified. A change in clinical management
reiterated the importance of a rapid genetic diagnosis by ES, after the report was observed in 44% patients. The diagnosis
which specifically helped in initiating therapy and changing the helped in targeted therapy in 12 patients (11%), palliative care
course of the illness. discussions in 14 patients (13%), and surveillance plans in 19
patients (18%). The authors underlined the need for more
Genome sequencing in pediatric heart disease (Genet Med.
evidence for assessing the clinical utility of ultra-rapid exome
2020;22:1015-24)
sequencing in other settings.
Congenital heart disease (CHD) is one of the most common
anomalies in humans. The Cardiac Genome Clinic was Genetic causes of neonatal encephalopathy (Clin Genet.
established in the Hospital for Sick Children, Canada, to assess 2020 Jul 26. 10.1111/cge.13818)
the utility of genome sequencing (GS) in children with heart Neonatal encephalopathy is a common condition that presents
diseases. Individuals from 111 families with cardiac diseases like in the newborn period with seizures, altered consciousness,
cardiomyopathy, laterality defects, and outflow tract poor muscle tone, and abnormal electroencephalogram, and
obstructions were recruited from January, 2017 to December, magnetic resonance imaging of the brain. The authors recruited
2018. Trio/ quartet (child and parents) GS was done and data 366 neonates with encephalopathy from 2015 to 2017, and
were generated for 328 individuals from 111 families. Using a performed trio/singleton exome sequencing. A definitive
specific research protocol for variant prioritization, candidate molecular diagnosis was established in 43 neonates (11.7%),
variants were identified. Causative pathogenic or likely with pathogenic or likely pathogenic variants. The variants were
pathogenic variants were identified in 14 of the 111 families identified in 30 genes which were classified into four different
(12.6%). Seven families had denovo variants in genes like categories: epileptic (58.5%), metabolic (18.9%), mitochondrial
ANKRD11 (KBG syndrome), KMT2D (Kabuki syndrome), (3.8%), and syndromic-related genes (18.9%). The most
NR2F2 (NR2F2- related CHD), POGZ (White-Sutton common genes to be involved were KCNQ2 and SCN2A, causing
syndrome), PTPN11 (Noonan syndrome), PTEN (PTEN epileptic encephalopathy. On follow up, it was observed that
hamartoma syndrome), and SALL1 (Townes-Brocks synd- death rate and severe development delay were higher in neonates
rome). Novel candidate genes for cardiac phenotypes identified with a genetic diagnosis. Several personalized therapeutic
in this cohort were FGD5, CDC42BPA, VASP or TLN2, TRPM4, interventions were possible in some of the genetic neonatal
SMARCC1, TPCN1, and UBXN10. Structural variants of sizes encephalopathies. Thus exome sequencing should be considered
ranging from 9.1kb to 8.3Mb were also identified and the in the workup of neonatal encephalopathy.
detection rate was more than chromosomal microarray. The
evidence generated in this study is likely to pave the way for GS DHANYA LAKSHMI N
as a first-tier diagnostic test for pediatric heart disease. dhanya.lakshmi@manipal.edu

I M A G E
Targetoid Hemosiderotic
Hemangioma
A 10-year-old boy presented with 1-year history of a gradually

progressive non-tender, soft-to-firm, dome-shaped, brownish-
black papule (6x6 mm) with a peripheral erythematous halo
situated above the umbilicus (Fig. 1). There was no history of
preceding trauma, acute illness or any drug intake. Other
mucocutaneous areas were uninvolved. Excision biopsy
confirmed the clinical impression of targetoid hemosiderotic
hemagioma (THH); no recurrence was noted on regular follow-
up.
THH is an acquired benign vascular lesion presenting as a
solitary, red-violaceous to brown targetoid papule with a
hemorrhagic halo; usually adolescent onset. Classic histology
shows biphasic pattern: dilated vessels lined by hobnail
endothelial cells with intraluminal papillae in the papillary Fig. 1 Targetoid hemosiderotic hemagioma characterized by a
dermis; and angulated and slit-like vascular spaces dissecting the dome-shaped, brownish-black papule with surrounding erythe-
collagen bundles in the reticular dermis, with plenty of matous halo.
extravasated erythrocytes and hemosiderin deposition at the
periphery (accounting for the targetoid appearance). They are
pubertal age, atypical melanocytic nests). Complete removal is
often misdiagnosed as melanocytic nevus (coarse hair, absence
sufficient to treat the condition.
of halo, presence of melanocytic nests), infantile hemangioma
(bright red lobulated plaque with typical growth pattern), AVIK PANIGRAHI* AND ABHEEK SIL
dermatofibroma (painful, positive dimpling sign), solitary Department of Dermatology, Venereology, and Leprosy,
angiokeratoma (no halo, hyperkeratosis and dilated vessels only RG Kar Medical College, Kolkata, West Bengal, India.
in papillary dermis on histology) or melanoma (rare in pre- *avik843@gmail.com
BOOK REVIEW
Principles of Pediatric and The book has eight sections along with annexures of drug
Neonatal Emergencies dosages. The chapters include all systemic emergencies along with
syndromic approach of many life-threatening conditions. A
Editor-in-Chief: PIYUSH GUPTA separate section on surgical emergencies along with approach to
Chief Academic Editors: ARVIND BAGGA injured child is relevant as most centers see many such cases in
AND SIDDARTH RAMJI day-to-day practice. Emergency procedures are explained well
Academic Editors: KRISHAN CHUGH along with pictorial assistance and ray diagrams.
AND RAKESH LODHA
M/s. Jaypee Brothers Medical Publishers This book is a ‘must read’ for all postgraduates and clinicians
(P) Ltd., New Delhi involved in the management of sick children.
Pages: 1000, Price: Rs. 1995/-
VIRENDRA KUMAR
The fourth edition of the Principles of Pediatric and Neonatal Director Professor & Head (Pediatrics)
Emergencies is a much awaited revised and updated version after Lady Hardinge Medical College and
nine years. This book is of immense importance as pediatric Kalawati Saran Children Hospital,
emergency medicine is an upcoming sub specialty of pediatrics in New Delhi, India.
India now. drvkumar1@gmail.com

ADVERTISEMENT

ADVERTISEMENT

ADVERTISEMENT

Printed and published by Dr Devendra Mishra on behalf of Indian Academy of Pediatrics and printed at
Cambridge Press, Kashmere Gate, Delhi-110006 and published at 115/4, Ground Floor,
Gautam Nagar, New Delhi 110 049. Editor: Dr Devendra Mishra

Indian Pediatrics October 2020 Issue

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Indian Pediatrics October 2020 Issue

Uploaded by

Copyright:

Available Formats

E-copy

Copyright of Indian Pediatrics.

INDIAN PEDIATRICS 883 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 884 VOLUME 57__OCTOBER 15, 2020

Editor-in-Chief Devendra Mishra CONTENTS

dIAP: Knowledge Sharing Amidst the Pandemic

INDIAN PEDIATRICS 887 VOLUME 57__OCTOBER 15, 2020

Fig.1 Trend of webinar numbers over the weeks.

INDIAN PEDIATRICS 888 VOLUME 57__OCTOBER 15, 2020

Fig. 2 Sub-specialty distribution of online teaching sessions on the dIAP platform.

Fig. 3 Features of an online platform.

INDIAN PEDIATRICS 889 VOLUME 57__OCTOBER 15, 2020

Sudden Unexpected Death in Epilepsy (SUDEP) - What Pediatricians

Published online: June 12, 2020; PII: S097475591600192

INDIAN PEDIATRICS 890 VOLUME 57__OCTOBER 15, 2020

include effects of long-standing seizure disorder such as

INDIAN PEDIATRICS 891 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 892 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 893 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 894 VOLUME 57__OCTOBER 15, 2020

Refining Clinical Triage and Management of Dengue Infection in Children:

INDIAN PEDIATRICS 895 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 896 VOLUME 57__OCTOBER 15, 2020

Identifying India’s Dual Nutrition Burden: Role of Body Mass Index

INDIAN PEDIATRICS 897 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 898 VOLUME 57__OCTOBER 15, 2020

WHO 2009 Warning Signs as Predictors of Time Taken for Progression to

INDIAN PEDIATRICS 899 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 900 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 901 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 902 VOLUME 57__OCTOBER 15, 2020

WHAT IS ALREADY KNOWN?

INDIAN PEDIATRICS 903 VOLUME 57__OCTOBER 15, 2020

Published online: June 12, 2020; PII: S097475591600197

INDIAN PEDIATRICS 904 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 905 VOLUME 57__OCTOBER 15, 2020

WHAT THIS STUDY ADDS?

INDIAN PEDIATRICS 906 VOLUME 57__OCTOBER 15, 2020

Progression of Thyrotropinemia in Overweight and Obese Children From

Correspondence to: Objective: To assess the progression of thyrotropinemia to overt hypothyroidism in

INDIAN PEDIATRICS 907 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 908 VOLUME 57__OCTOBER 15, 2020

WHAT THIS STUDY ADDS?

REFERENCES 9. Wasniewska M, Corrias A, Aversa T, Valenzise M, Mussa

INDIAN PEDIATRICS 909 VOLUME 57__OCTOBER 15, 2020

Weight of Schoolbags Among Indian Schoolchildren in Pune and Hyderabad

INDIAN PEDIATRICS 910 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 911 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 912 VOLUME 57__OCTOBER 15, 2020

WHAT THIS STUDY ADDS?

Indian Pediatrics Case Reports (IPCaRes)

Submit Your Manuscripts at the Earliest

Epidemiological and Clinical Characteristics of COVID-19 in Indian

Published online: July 28, 2020; PII: S097475591600218

INDIAN PEDIATRICS 914 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 915 VOLUME 57__OCTOBER 15, 2020

WHAT THIS STUDY ADDS?

INDIAN PEDIATRICS 916 VOLUME 57__OCTOBER 15, 2020

www.who.int/publications-detail/global-surveillance-for- 10. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N,

INDIAN PEDIATRICS 917 VOLUME 57__OCTOBER 15, 2020

Maternal Occupational Tobacco Exposure and Newborn Umbilical Cord

INDIAN PEDIATRICS 918 VOLUME 57__OCTOBER 15, 2020

INDIAN PEDIATRICS 919 VOLUME 57__OCTOBER 15, 2020

WHAT THIS STUDY ADDS?